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Use of Win-Stay and Win-Shift Strategies in Place and Cue Tasks by Medial Caudate Putamen (MCPu) Lesioned Rats
Abstract
This study investigated the behavioral function of the medial caudate putamen (MCPu) in the solving of maze tasks. MCPu lesioned rats (n = 35) and control rats (n = 35) were trained for the place or cue task (the four baited arms and four unbaited arms task) in an eight-arm radial maze, which requires the win-stay or the win-shift strategy. In Experiment 1, in which the place task was used, MCPu lesioned rats could learn the task in the win-shift condition, but not in the win-stay condition. MCPu lesioned rats made a lot of unbaited errors in the win-stay condition, as they persistently chose adjacent arms. Control rats could learn the tasks in both conditions. In Experiment 2, in which the cue task was used, MCPu lesioned rats and control rats could learn the tasks in both the win-stay and the win-shift conditions. If anything, the performance of MCPu rats was a little better than that of control rats in the win-stay condition. The results of these two experiments revealed that the MCPu was involved in solving the win-stay place task, but not the win-shift place, win-stay cue, and win-shift cue tasks. These findings suggest that the MCPu plays an important role in utilizing both spatial information and switching foraging strategies flexibly and efficiently, that is, processing complicated visuospatial cognition.
... The basic design of the win–shift procedure and approach to data analysis was derived from previous investigations (Floresco, Seamans, & Phillips, 1996, 1997 Packard & Chen, 1999; Packard, Regenold, Quiron, & White, 1990; Packard & White, 1991; Sage & Knowlton, 2000; Sakamoto & Okaichi, 2001; White, Packard, & Seamans, 1993). The testing room contained extra-maze cues, including several posters; dark-colored shapes, such as an L and an X, a lamp; door; sink; cabinet; table; and two experimenters. ...
... Our findings that suggest mild long-term hippocampal dysfunction appear consistent with other reports of behavior of formerly ID children (DeBoer, Wewerka, Bauer, Georgieff, & Nelson, 2005; Nelson et al., 2000) and confirm the findings of Felt and Lozoff (1996), who demonstrated deficits in the spatial navigation skills of prenatally ID adult animals, and of McEcheron, Cheng, Liu, Connor, and Gilmartin (2005) , who demonstrated abnormal trace conditioning in formerly ID rats. Although the hippocampus is the most common brain region associated with impairments in spatial and recognition memory, some research implicates other structures, like the medial caudate putamen (MCPu), in spatial/place learning tasks such as the win–shift procedure (DeCoteau, Hoang, Huff, Stone, & Kesner, 2004; Devan, McDonald, & White, 1999; Sakamoto & Okaichi, 2001; Smith-Roe, Sadeghian, & Kelley, 1999). However, diminished function of the MCPu is not thought to underlie the deficits noted in the present study. ...
... However, diminished function of the MCPu is not thought to underlie the deficits noted in the present study. This is because previous investigations in which impairments/delays in win–shift learning following MCPu damage have been found, also described impairments/delays on stimulus response, cue-based win–stay learning ( Sakamoto & Okaichi, 2001). Therefore, if the root of the deficit in the FID rats was due to MCPu dysfunction, potentially due to early ID-induced dopaminergic/striatal effects, deficits in win–stay learning should also have been observed in the present study. ...
Iron deficiency (ID) is a common nutrient deficiency worldwide. This condition is linked to changes in myelin formation, dopaminergic function, and energy metabolism. Early ID results in persistent long-term cognitive and behavioral disturbances in children, despite a return to normal iron status. The present study assesses formerly ID adult rats on maze learning tasks that depend on specific brain regions related to learning, specifically the hippocampus, striatum, and amygdala. Rat dams were fed ID chow starting on gestational Day 2 through postnatal Day 7, and behavioral testing began at postnatal Day 65--following a return to normal iron status. Formerly ID rats exhibited delayed acquisition of the hippocampus-dependant task and no differences from controls on the striatum- and amygdala-dependent tasks. These findings likely reflect long-term reduction in but not abolition of hippocampus-dependent learning and preserved function in other brain structures (e.g., striatum and amygdala).
... A number of investigators have noticed such differences in connectivity, and conducted studies to test the hypothesis that the DMS is also involved in behavioral flexibility and spatial learning Sakamoto and Okaichi 2001;Ragozzino 2003). For example, on a hiddenplatform water maze task, lesions of the DMS impaired the use of distal spatial cues in navigation, resulting in a preference for use of S-R memory when competing place-and cue-learning preferences were simultaneously assessed (Whishaw et al. 1987;. ...
... On the basis of the present results as well as results from other studies (Whishaw et al. 1987;Sakamoto and Okaichi 2001), we propose that both the hippocampal formation and the PDMS are components of a larger corticostriatal system mediating flexible, goal-directed responding based on an integrated representation of the environment. This view is an extension of the widely accepted claim that, in the cerebral hemispheres, the functional unit capable of integrated behavioral functions is neither a part of cortex nor a part of striatum, but rather a corticobasal ganglia circuit (Alexander et al. 1986;Alexander and Crutcher 1990). ...
The involvement of different subregions of the striatum in place and response learning was examined using a T-maze. Rats were given NMDA lesions of the dorsolateral striatum (DLS), anterior dorsomedial striatum (ADMS), posterior dorsomedial striatum (PDMS), or sham surgery. They were then trained to retrieve food from the west arm of the maze, starting from the south arm, by turning left at the choice point. After 7 d of training, with four trials a day, a probe test was given in which the starting arm is inserted as the north arm, at the opposite side of the maze. A left turn would indicate a "response" strategy; a right turn, a "place" strategy. The rats were then trained for 7 more days, followed by a second probe test. Unlike rats in the other groups, most of the rats in the PDMS group turned left, using the response strategy on both probe tests. These results suggest that the PDMS plays a role in spatially guided behavior.
... A comparison between performance in the Y-maze and the radial maze also led us to the same conclusion. Increasing the number of options in the radial maze (eight options instead of the two in the Y-maze) also reveals a deficit in rats with dorsal striatal lesion (Kantak, Green-Jordan, Valencia, Kremin, & Eichenbaum, 2001; Packard et al., 1989; McDonald & White, 1991; Sakamoto & Okaichi, 2001). 3.2.1. ...
... Such a situation requires the BG to suppress the expression of the prepotent response, and support the selection of a more adaptive one. In fact, the evidence suggests that even when the animal is given two choices (e.g., the Y-maze), a disruption of the BG impairs the performance of reversal and strategy-switching tasks (Ragozzino et al., 2002b; Ragozzino, Jih, & Tzavos, 2002a; Sakamoto & Okaichi, 2001; Wishaw et al., 1987). For example, Ragozzino et al., 2002a reported that the inactivation of the dorsomedial striatum does not affect the acquisition of a response task (i.e., making a left turn in the four-arm plus maze). ...
We present a framework for understanding how the hippocampus, neocortex, and basal ganglia work together to support cognitive and behavioral function in the mammalian brain. This framework is based on computational tradeoffs that arise in neural network models, where achieving one type of learning function requires very different parameters from those necessary to achieve another form of learning. For example, we dissociate the hippocampus from cortex with respect to general levels of activity, learning rate, and level of overlap between activation patterns. Similarly, the frontal cortex and associated basal ganglia system have important neural specializations not required of the posterior cortex system. Taken together, this overall cognitive architecture, which has been implemented in functioning computational models, provides a rich and often subtle means of explaining a wide range of behavioral and cognitive neuroscience data. Here, we summarize recent results in the domains of recognition memory, contextual fear conditioning, effects of basal ganglia lesions on stimulus-response and place learning, and flexible responding.
... The type of learning undertaken in this latter task requires that the animal forms associations between stimuli and responses, or habit learning. Others have identified the striatum as important to this type of learning [1] [2]. ...
... The habit-learning task differed from that used by McDonald and White [7]; however, since PSWs are task and species specific [3], we used the same version of the RAM that was used to determine the PSW. Others have previously used the four-arm baited paradigm to investigate habit learning [2]. Numerous studies have shown that post-training drug injections impair learning. ...
Systemic treatments with acetylcholine (ACh) or dopamine (DA) receptor antagonists during hours 0-4 but not during hours 5-8 following training on a radial arm maze (RAM) or lesions of the dorsal striata impair learning. This suggested that intra-striatal infusions of ACh or DA receptor antagonists during hours 0-4 following training may impair learning. Rats were randomly assigned to groups (ns=5-11) receiving dorsal striatal infusions of the ACh receptor antagonist scopolamine (0-18 microg/microL at 0 and 2h or at 4 and 6h after training), the DA receptor antagonist cis-flupenthixol (0-25 microg/microL at 0, 4 or 12h after training) or the inactive isomer trans-flupenthixol (6 microg/microL at 0 h after training). Scopolamine and cis-flupenthixol impaired the habit-learning version of the task. Given after hours 0-4 following training, the effects of scopolamine were diminished but those of cis-flupenthixol were not. Trans-flupenthixol produced less impairment than cis-flupenthixol. Results suggest that ACh and DA receptors in the dorsal striatum during hours 0-4 following training play a role in habit learning.
... Similarly, in rodents, spontaneous variation in foraging patterns are common, even following reinforcement of prior exploration (a win-shift pattern, [68,69]. Non-specific lesions of dorsal striatum impair this behavioral variability and can increase spontaneous alternation in 'win-stay' conditions, where rodents need to return to previously rewarded areas [70,71]. Future studies could investigate striatal patches as a site for stabilizing behavioral patterns in motor behaviors and reinforcement learning beyond operant conditioning. ...
Habits are automated behaviors that are insensitive to changes in behavioral outcomes. Habitual responding is thought to be mediated by the striatum, with medial striatum guiding goal-directed action and lateral striatum promoting habits. However, interspersed throughout the striatum are neurochemically differing subcompartments known as patches, which are characterized by distinct molecular profiles relative to the surrounding matrix tissue. These structures have been thoroughly characterized neurochemically and anatomically, but little is known regarding their function. Patches have been shown to be selectively activated during inflexible motor stereotypies elicited by stimulants, suggesting that patches may subserve habitual behaviors. To explore this possibility, we utilized transgenic mice (Sepw1 NP67) preferentially expressing Cre recombinase in striatal patch neurons to target these neurons for ablation with a virus driving Cre-dependent expression of caspase 3. Mice were then trained to press a lever for sucrose rewards on a variable interval schedule to elicit habitual responding. Mice were not impaired on the acquisition of this task, but lesioning striatal patches disrupted behavioral stability across training, and lesioned mice utilized a more goal-directed behavioral strategy during training. Similarly, when mice were forced to omit responses to receive sucrose rewards, habitual responding was impaired in lesioned mice. To rule out effects of lesion on motor behaviors, mice were then tested for impairments in motor learning on a rotarod and locomotion in an open field. We found that patch lesions partially impaired initial performance on the rotarod without modifying locomotor behaviors in open field. This work indicates that patches promote behavioral stability and habitual responding, adding to a growing literature implicating striatal patches in stimulus-response behaviors.
... Las ratas consumieron en el lugar de encuentro los trozos pequeños de comida y transportaron lo trozos grandes independientemente de la distancia y la dispersión. Por otra parte, cuando los animales son expuestos a dos zonas de búsqueda de alimento el cambio de zona es favorecido a medida que disminuye la cantidad de alimento de la zona en la que se encuentra (Haig, Rawlins, Olton, Mead, & Taylor, 1983;Laughlin & Mendl, 2000;Sakamoto & Okaichi, 2001). ...
The distribution of food has not been widely studied in the areas of foraging and patch choice. Search time and the potential exposure to predators vary when animals are exposed to two patches that have similar food density but different food distribution. The effects of food dispersion on choice, exploration, and exploitation of two patches was studied. A group of rats was placed in an experimental apparatus that had a choice area and two patches that were topographically identical and contained the same amount of food but varied in food dispersion: either the food was concentrated in a single place or the food was dispersed in eight different locations. Results showed that the rats remained a longer time in the concentrated patch and showed shorter, exhaustive visits to the patch where the food was dispersed. Rats developed different exploration patterns for each of the areas. The preferred areas for exploration were both the choice area and the concentrated patch.
... alternation behavior and reversal learning (Rosvold, 1968;Divac et al., 1967Divac et al., , 1972Kolb, 1977; for reviews, see Iversen, 1979;Oberg and Divac, 1979). In rats, damage to the medial dorsal striatum can in some cases produce cognitive learning deficits fairly similar to those observed following hippocampal system damage (e.g., Divac, 1968;Kolb, 1977;Whishaw et al., 1987;; but see also Sakamoto and Okaichi, 2001;Packard and McGaugh, 1992;DeCoteau and Kesner, 2000;Adams et al., 2001). Consistent with the idea that medial and lateral regions of the dorsal striatum are differentially involved in learning and memory, lesions of the posterior dorsomedial, but not the DLS, block the ability of reinforcer devaluation to reduce instrumental responding (Yin et al., , 2005Corbit et al., 2012;Quinn et al., 2013). ...
... Little is known about the neural basis of the response strategies used for resolving a given problem in a cognitive task 24,25 . However, a number of studies have pointed out the involvement of some key structures such as the hippocampal system 26,27,28 , the caudate nucleus 27 , the prefrontal cortex 29,30,31 and the putamen 32 . ...
The number of studies that use the common marmoset (Callithrix jacchus) in various fields of neurosciences is increasing dramatically. In general, animals enter the study when their health status is considered satisfactory on the basis of classical clinical investigations. In behavioral studies, variations of score between individuals are frequently observed, some of them being considered as poor performers or outliers. Experimenters rarely consider the fact that it could be related to some brain anomaly. This raises the important issue of the reliability of such classical behavioral approaches without using complementary imaging, especially in animals lacking striking external clinical signs. Here we report the case of a young marmoset which presented a set of cognitive impairments in two different tasks compared to other age-matched animals. Brain imaging revealed a patent right lateral ventricular enlargement with a mild hippocampal atrophy. This abnormality could explain the cognitive impairments of this animal. Such a case points to the importance of complementing behavioral studies by imaging explorations to avoid experimental bias.
... DLS lesions produced the opposite effect in both tasks (Mair, Koch, Newman, Howard, & Burk, 2002). Win-stay and win-shift strategies have also been studied specifically in rats with DMS lesions (Sakamoto & Okaichi, 2001). This study found that the DMS was critical for the win-stay place task, but not for the win-shift place, win-stay cue, or win-shift cue tasks. ...
... Las ratas consumieron en el lugar de encuentro los trozos pequeños de comida y transportaron lo trozos grandes independientemente de la distancia y la dispersión. Por otra parte, cuando los animales son expuestos a dos zonas de búsqueda de alimento el cambio de zona es favorecido a medida que disminuye la cantidad de alimento de la zona en la que se encuentra (Haig, Rawlins, Olton, Mead, & Taylor, 1983;Laughlin & Mendl, 2000;Sakamoto & Okaichi, 2001). ...
Deciding both, whether a response sequence is a different behavioral unit than the elements that constitute it, and if it obeys the same reinforcement rules than discrete responses, has been a difficult problem. A way to prove that a sequence is a behavioral unit is to determine if it behaves according to the principles of the matching law. With this purpose, four naïve experimentally rats were food-deprived and trained to lever press two operanda in a sequence to receive a drop of milk. Different concurrent variable interval (VI) schedules were used to reinforce each of four possible sequences. When the rats produced a non-reinforced sequence the lights of the experimental chamber were turned off during 2 s. In three consecutive phases of the experiment, the reinforcement rate for each sequence was different. Results showed that the rats were highly sensitive to the relative rates of reinforcement assigned to each sequence. However, the adjustment curves showed slopes that were smaller than one, thus under-matching was found. It was concluded that although a response sequence can behave as an integrated pattern of behavior, it does not necessarily represent an equivalent behavioral unit comparable to that of a discrete operant response.
... Las ratas consumieron en el lugar de encuentro los trozos pequeños de comida y transportaron lo trozos grandes independientemente de la distancia y la dispersión. Por otra parte, cuando los animales son expuestos a dos zonas de búsqueda de alimento el cambio de zona es favorecido a medida que disminuye la cantidad de alimento de la zona en la que se encuentra (Haig, Rawlins, Olton, Mead, & Taylor, 1983;Laughlin & Mendl, 2000;Sakamoto & Okaichi, 2001). ...
The distribution of food has not been widely studied in the areas of foraging and patch choice. Search time and the potential exposure to predators vary when animals are exposed to two patches that have similar food density but different food distribution. The effects of food dispersion on choice, exploration, and exploitation of two patches was studied. A group of rats was placed in an experimental apparatus that had a choice area and two patches that were topographically identical and contained the same amount of food but varied in food dispersion: either the food was concentrated in a single place or the food was dispersed in eight different locations. Results showed that the rats remained a longer time in the concentrated patch and showed shorter, exhaustive visits to the patch where the food was dispersed. Rats developed different exploration patterns for each of the areas. The preferred areas for exploration were both the choice area and the concentrated patch.
... Although the functional heterogeneities of striatum (dorsomedial striatum for spatial learning and dorsolateral for S-R type learning), as they are described in the present model, have significant experimental support, there are several exceptions to the rule. For example, in radial maze learning studies involving lesions of dorsal lateral and medial striatum [64] and lesions specific to dorsomedial striatum [65], hippocampus-dependent spatial learning was not impaired. Also in several other water maze studies [1], [66], dorsomedial striatal lesions did not completely block spatial learning. ...
A computational neural model that describes the competing roles of Basal Ganglia and Hippocampus in spatial navigation is presented. Model performance is evaluated on a simulated Morris water maze explored by a model rat. Cue-based and place-based navigational strategies, thought to be subserved by the Basal ganglia and Hippocampus respectively, are described. In cue-based navigation, the model rat learns to directly head towards a visible target, while in place-based navigation the target position is represented in terms of spatial context provided by an array of poles placed around the pool. Learning is formulated within the framework of Reinforcement Learning, with the nigrostriatal dopamine signal playing the role of Temporal Difference Error. Navigation inherently involves two apparently contradictory movements: goal oriented movements vs. random, wandering movements. The model hypothesizes that while the goal-directedness is determined by the gradient in Value function, randomness is driven by the complex activity of the SubThalamic Nucleus (STN)-Globus Pallidus externa (GPe) system. Each navigational system is associated with a Critic, prescribing actions that maximize value gradients for the corresponding system. In the integrated system, that incorporates both cue-based and place-based forms of navigation, navigation at a given position is determined by the system whose value function is greater at that position. The proposed model describes the experimental results of [1], a lesion-study that investigates the competition between cue-based and place-based navigational systems. The present study also examines impaired navigational performance under Parkinsonian-like conditions. The integrated navigational system, operated under dopamine-deficient conditions, exhibits increased escape latency as was observed in experimental literature describing MPTP model rats navigating a water maze.
... [34][35][36][37][38]; but see also refs. [39,40]). ...
The plus-maze apparatus figured prominently in the historical debate between cognitive and stimulus-response habit learning theorists concerned with the fundamental question of "what" animals learn. An important feature of this task is that variants of the training procedure can be arranged to allow for an assessment of the relative use of cognitive/place or habit/response learning mechanisms. This brief review describes findings from several neurobiological studies published primarily over the past decade that have re-introduced the plus-maze to investigate the role of the dorsal striatum in learning and memory. Converging evidence from research using brain lesion, pharmacological, and molecular/genetic approaches is described supporting the hypothesis that the dorsolateral striatum plays a selective role in response learning in the plus-maze. Within a multiple systems framework of memory organization, factors that can influence the relative use of place and response learning in the plus-maze are also considered, including the nature of the visual environment, reinforcement/training parameters, and emotional state of the organism. Response learning in the plus-maze may be considered an exemplar task useful for investigating the neurobiological bases of dorsal striatal involvement in habit learning and memory. This mnemonic function of the dorsal striatum generalizes across several sensory modalities and mammalian species, including humans.
... Moreover, there is behavioral evidence that appears inconsistent with the idea that medial dorsal striatal lesions produce mnemonic deficits identical to those produced by hippocampal system lesions. For example, large lesions of the dorsal striatum that include lateral and medial regions (Packard et al. 1989Packard et al. , 1992), as well as lesions restricted to the medial dorsal striatum (Sakamoto & Okaichi 2001), do not impair acquisition of hippocampus-dependent win-shift behavior in the radial maze. Moreover, in the previously described spatial and S-R visual-discrimination water maze tasks (Packard & McGaugh 1992 ), medial dorsal striatal lesions selectively impaired acquisition of the S-R task, whereas fimbria-fornix lesions produced the opposite effect. ...
Although the mammalian basal ganglia have long been implicated in motor behavior, it is generally recognized that the behavioral functions of this subcortical group of structures are not exclusively motoric in nature. Extensive evidence now indicates a role for the basal ganglia, in particular the dorsal striatum, in learning and memory. One prominent hypothesis is that this brain region mediates a form of learning in which stimulus-response (S-R) associations or habits are incrementally acquired. Support for this hypothesis is provided by numerous neurobehavioral studies in different mammalian species, including rats, monkeys, and humans. In rats and monkeys, localized brain lesion and pharmacological approaches have been used to examine the role of the basal ganglia in S-R learning. In humans, study of patients with neurodegenerative diseases that compromise the basal ganglia, as well as research using brain neuroimaging techniques, also provide evidence of a role for the basal ganglia in habit learning. Several of these studies have dissociated the role of the basal ganglia in S-R learning from those of a cognitive or declarative medial temporal lobe memory system that includes the hippocampus as a primary component. Evidence suggests that during learning, basal ganglia and medial temporal lobe memory systems are activated simultaneously and that in some learning situations competitive interference exists between these two systems.
... These data suggest that the maze geometry is encoded and stored during maze tasks. (v) It is noticeable that rodents naturally develop uncontrolled strategies to solve spatial tasks [11,13,14,16,28,30] and that these strategies may mask the processes originally targeted. (vi) In this context, we propose a new simple maze paradigm challenging place learning in rats that controls the strategy used by the animals. ...
The present work defines a simple behavioral paradigm to evaluate spatial representation in rats. In two experimental conditions differing in the richness of distal visual cues, rats learned to locate a food goal in a cross maze from various starting points. We conducted different challenges consisting of (i) reaching the same goal from a modified arrangement of the maze arms (geometric challenge), (ii) reaching the goal within a 90 degrees rotated maze, herein checking the use of a place strategy, and (iii) investigating the effect of central cholinergic blockade over the retention of the task. Results showed that rats needed 12-30 trials to learn a place response, depending upon the richness of the visual environment. The maze rotation did not produce any impairment whereas the geometric challenge affected the performance specifically under the visually richer environment. Scopolamine injection (i.p.) produced a significant impairment in place recognition. Our present work shows that this maze procedure constitutes a useful paradigm to assess learning and processing of a place representation by rats. Similarly to what has been shown in other popular maze paradigms, our results show that rats mostly rely on distal extra-maze cues to solve the task, but also compute intra-maze information.
... Last, this lesion technique allowed for direct comparisons with the work of others (e.g. Devan et al., 1996;McDonald and White, 1993;Sakamoto and Okaichi, 2001). ...
Depending on task demands, there is a growing body of evidence suggesting that the dorsal striatum plays a critical role in not only learning new response strategies but also in the inhibition of pre-existing strategies when a shift in strategy is required. The present experiment examined the effects of lesions of the dorsal striatum or dorsal hippocampus on acquisition of a response-learning rule and a place-learning rule in a Greek Cross version of the Morris water maze. Specifically, adult Long-Evans rats were prepared with either sham lesions or lesions to one of two subcortical areas of the brain considered necessary for processing nondeclarative or declarative memories, the dorsal striatum or the hippocampus, respectively. An analysis of the trial 2 performance pooled across reversals revealed hippocampus lesions induced accelerated acquisition when a response-learning rule was required. A much smaller enhancement effect was observed in dorsal striatum-lesioned animals in the place-learning paradigm. Dorsal hippocampus- and dorsal striatum-lesioned animals were highly impaired on place learning and response learning, respectively. The present results are congruent with a growing body of literature suggesting that different anatomical substrates are involved in the acquisition and maintenance of different types of information, that these processes can occur simultaneously and in parallel, and that the dorsal striatum is necessary for the mediation of stimulus-response learning, while the hippocampus is necessary to mediate the expression of place learning.
... Other Wndings indicate that in a spatial water maze task-a task that allows for assessment of learning using choice behavior in addition to latency measuresacquisition is normal in rats with medial dorsal striatal damage (Packard & McGaugh, 1992). Moreover, lesions of the medial dorsal striatum do not impair hippocampus-dependent spatial memory in a radial maze (Sakamoto & Okaichi, 2001). In the present study, IEG activation in the medial aspect of the dorsal striatum occurred in all rats that swam in the maze, independent of the type of task (spatial or cued) that animals were trained on. ...
Research examining the neuroanatomical bases of memory in mammals suggests that the hippocampus and dorsal striatum are parts of independent memory systems that mediate "cognitive" and stimulus-response "habit" memory, respectively. At the molecular level, increasing evidence indicates a role for immediate early gene (IEG) expression in memory formation. The present experiment examined whether acquisition of cognitive and habit memory result in differential patterns of IEG protein product expression in these two brain structures. Adult male Long-Evans rats were trained in either a hippocampal-dependent spatial water maze task, or a dorsal striatal-dependent cued water maze task. Ninety minutes after task acquisition, brains were removed and processed for immunocytochemical procedures, and the number of cells expressing Fos-like immunoreactivity (Fos-like-IR) and c-Jun-IR in sections from the dorsal hippocampus and the dorsal striatum were counted. In the dorsal hippocampus of rats trained in the spatial task, there were significantly more c-Jun-IR pyramidal cells in the CA1 and CA3 regions, relative to rats that had acquired the cued task, yoked controls (free-swim), or naïve (home cage) rats. Relative to rats receiving cued task training and control conditions, increases in Fos-like IR were also observed in the CA1 region of rats trained in the spatial task. In rats that had acquired the cued task, patches of c-Jun-IR were observed in the posteroventral striatum; no such patches were evident in rats trained in the spatial task, yoked-control rats, or naïve rats. The results demonstrate that IEG protein product expression is up-regulated in a task-dependent and brain structure-specific manner shortly after acquisition of cognitive and habit memory tasks.
... Although the results of numerous investigations have not yielded uniform findings, the weight of evidence supports the contention that under appetitive motivation, win-shift strategies are acquired more rapidly than are win-stay strategies (Locurto et al., 2002). These behavioral differences have been underscored by the suggestion that different neurologic mechanisms may subserve each procedure (e.g., McDonald & White, 1993;Packard & White, 1990;Sakamoto & Okaichi, 2001). There has also been speculation that each procedure may require subjects to rely principally on different associative mechanisms: stimulus-response learning in the case of win-stay learning and stimulus-stimulus learning in the case of win-shift learning (Sage & Knowlton, 2000). ...
Previous research (C. Locurto, C. Emidy, & S. Hannan, 2002) indicated that mice quickly learned a water-escape task under a win-shift contingency but did not exceed chance-level performance under a win-stay contingency. We examined the robustness of this conclusion in two experiments by varying procedural and temporal aspects of that earlier experiment. Results of both experiments indicated that the preference for win-shift learning in mice under water-escape motivation could not be attributed to procedural or design features of that earlier study and were independent of the influence of intertrial interval, normally a variable that produces strong effects on learning. In neither experiment did subjects exposed to a win-stay contingency perform at above-chance levels.
... In rodents, lesions of the dorsal striatum (STR) result in spatial learning deficits (Devan, McDonald, & White, 1999; Sakamoto & Okaichi, 2001). In addition, striatal place fields have been identified (Mizumori et al., 1999, Mizumori, Cooper, et al., 2000), and these, like hippocampal place fields, change locations, or reorganize , after alterations in spatial context (Yeshenko, Guazzelli, & Mizumori, 2004). ...
Place-specific firing by hippocampal and striatal neurons was recorded simultaneously following injection of a D(1) receptor antagonist (SCH23390) and during spatial working memory task performance. SCH23390-induced changes in unit responses were observed during light and dark test conditions. Although hippocampal place field locations were altered by the contextual change, the reliability and specificity of place fields was disrupted only by combining D(1) antagonism and a change in context. Striatal place field locations were reorganized after either contextual change or D(1) antagonism, without altering place field reliability and specificity. Disrupted velocity encoding by place cells in both regions was induced by darkness, whereas greater stability in acceleration encoding followed removal of D(1) receptor activity. Dopamine may differentially regulate hippocampal context learning and striatum-based predictive codes.
Habits are automated behaviors that are insensitive to changes in behavioral outcomes. Habitual responding is thought to be mediated by striatum, with medial striatum guiding goal-directed action and lateral striatum promoting habits. However, interspersed throughout the striatum are neurochemically differing subcompartments known as patches, which are characterized by distinct molecular profiles relative to the surrounding matrix tissue. These structures have been thoroughly characterized neurochemically and anatomically, but little is known regarding their function. Patches have been shown to be selectively activated during inflexible motor stereotypies elicited by stimulants, suggesting that patches may subserve habitual behaviors. To explore this possibility, we utilized transgenic mice ( Sepw1 NP67) expressing Cre recombinase in striatal patches to target these neurons for selective ablation with a virus driving Cre-dependent expression of caspase 3. Mice were then trained to press a lever for sucrose rewards on a variable interval schedule to elicit habitual responding. Mice were not impaired on the acquisition of this task, but lesioning striatal patches disrupted behavioral stability across training and lesioned mice utilized a more goal-directed behavioral strategy during training. Similarly, when mice were forced to omit responses to receive sucrose rewards, habitual responding was impaired in lesioned mice. To rule out effects of lesion on motor behaviors, mice were then tested for impairments in motor learning on a rotarod and locomotion in an open field. We found that patch lesions specifically impaired initial performance on the rotarod without modifying locomotor behaviors in open field. This work indicates that patches promote behavioral stability and habitual responding, adding to a growing literature implicating striatal patches in stimulus-response behaviors.
Procedural learning and memory involves the acquisition, consolidation, and retrieval of individual representations that are behaviorally expressed in an inflexible manner. Stimulus–response habit learning represents a prominent form of procedural learning in the mammalian brain. Extensive evidence supports the hypothesis that this form of procedural learning is mediated by a neural system that contains the dorsal striatum as a primary component. Studies employing brain lesion techniques have dissociated the roles of the dorsal striatum and hippocampus in procedural and declarative memory, respectively. Pharmacological studies indicate a selective role for dorsal striatal dopamine, acetylcholine, and glutamate in memory consolidation underlying stimulus–response procedural learning.
This chapter reviews evidence supporting the hypothesis that the basal ganglia mediate a form of learning in which hullian-like stimulus-response (S-R) habits are acquired and expressed. This idea has largely been developed within the context of a multiple systems approach to memory organization. According to multiple memory systems theory, relatively independent brain systems support the acquisition of different types of memory. The chapter provides an overview of data supporting this hypothesis by focusing on evidence that the selective role of the basal ganglia in habit learning and memory generalizes across different mammalian species, including rats, monkeys, and humans. The chapter provides converging evidence for this view of the mnemonic function of the basal ganglia by highlighting a few prominent experiments from each of these species. Review of the findings from lower animals (rats and non-human primates) focuses on lesion studies, whereas description of the human research focuses on research involving patients with neuropsychological disorders and neuroimaging studies.
In the present study, we examined whether oxidative stress in the hippocampus contributes to memory deficits induced by unilateral injections of two different doses of lipopolysaccharide (3μg/kg and 10μg/kg) into the substantia nigra of adult male Wistar rats. Pergolide-induced rotational behavior test was employed to validate unilateral damage to the dopamine nigrostriatal neurons. Lipopolysaccharide-induced memory impairments were observed, as measured by the Y-maze and radial arm-maze tasks. Decreased activities of superoxide dismutase and glutathione peroxidase were observed in the rat hippocampal homogenates of lipopolysaccharide-treated animals as compared with control. Production of malondialdehyde (lipid peroxidation) significantly increased in the rat hippocampal homogenates of lipopolysaccharide-treated animals as compared with control, as a consequence of impaired antioxidant enzymes activities. Additionally, only within Y-maze, significant correlations between behavioral deficits and indicators of oxidative stress were found. However, further studies are necessary in order to elucidate the effects of intranigral lipopolysaccharide administration on memory performance and oxidative stress status and also the possible correlation that might exist between these aspects.
The multiple memory systems hypothesis posits that dorsal striatum and hippocampus are central nodes in independent memory sys-tems, supporting response-based and place-based learning, respec-tively. Although our understanding of the function of hippocampus within this framework is relatively well established, the contribution of dorsal striatum is less clear. This in part seems to be due to the heterogeneous nature of dorsal striatum, which receives extensive topographically organized projections from higher cortical areas. Here we quantified neural activity in the intact brain while mice and humans acquired analogous versions of the Morris water maze. We found that dorsomedial striatum and medial prefrontal cortex support the initial acquisition of what is typically considered a hippocampus-dependent spatial learning task. We suggest that the circuit involving dorsomedial striatum and medial prefrontal cortex identified here plays a more task-independent role in early learning than currently thought. Furthermore, our results demonstrate that dorsomedial and dorsolateral striatum serve fundamentally differ-ent roles during place learning. The remarkably high degree of anatomical overlap in brain function between mouse and human observed in our study emphasizes the extent of convergence achiev-able with a well-matched multilevel approach. functional MRI | immediate early gene | navigation
The multiple memory systems hypothesis posits that dorsal striatum and hippocampus are central nodes in independent memory systems, supporting response-based and place-based learning, respectively. Although our understanding of the function of hippocampus within this framework is relatively well established, the contribution of dorsal striatum is less clear. This in part seems to be due to the heterogeneous nature of dorsal striatum, which receives extensive topographically organized projections from higher cortical areas. Here we quantified neural activity in the intact brain while mice and humans acquired analogous versions of the Morris water maze. We found that dorsomedial striatum and medial prefrontal cortex support the initial acquisition of what is typically considered a hippocampus-dependent spatial learning task. We suggest that the circuit involving dorsomedial striatum and medial prefrontal cortex identified here plays a more task-independent role in early learning than currently thought. Furthermore, our results demonstrate that dorsomedial and dorsolateral striatum serve fundamentally different roles during place learning. The remarkably high degree of anatomical overlap in brain function between mouse and human observed in our study emphasizes the extent of convergence achievable with a well-matched multilevel approach.
The ‘stop-signal’ task measures the ability to inhibit a response that has already been initiated, i.e. the ability to stop. Human subjects who have been classified as ‘impulsive’, for example, those with attention-deficit/hyperactivity disorder (ADHD), are slower to react to the stop signal, and are often less sensitive to changes in the timing of signals to stop. Imaging studies have implicated fronto-striatal circuitry in the mediation of this form of response control.We report inhibition functions on the stop-signal reaction time (SSRT) task for normal rats, and following damage to the medial prefrontal cortex or to the nucleus accumbens core. Neither group of excitotoxic lesions produced significant deficits on task performance. Subsequent treatment with d-amphetamine (0.3 and 1.0 mg/kg) resulted in quicker go-trial reaction times (mRT) overall, but had no significant effect on SSRT. Neither medial prefrontal cortex nor nucleus accumbens lesions had any differential effects on performance following d-amphetamine. These results are discussed with respect to the fronto-striatal circuitry involved in the mediation of behavioural inhibition.
The stop-signal task measures the ability to inhibit a response that has already been initiated, that is, the ability to stop. Imaging studies have implicated frontostriatal circuitry in the mediation of this form of response control. The authors report inhibition functions of normal rats and those with medial striatal damage performing the stop-signal task. Excitotoxic lesions of the medial striatum produced significant deficits on task performance, including increased omissions on the go task and flattened inhibition function, possibly as a result of increased reaction-time mean and variability. Medial striatal lesions also significantly slowed stop-signal reaction time. Subsequent treatment with d-amphetamine removed (0.3 mg/kg) or exacerbated (1.0 mg/kg) this deficit.
These experiments addressed the role of striatal N-methyl-D-aspartate (NMDA) receptors in spatial behavior in the radial arm maze. Rats treated with the NMDA antagonist D-2-amino-5-phosphonopentanoic acid (AP-5) in the nucleus accumbens core, medial caudate, and posterior caudate were all significantly impaired in acquiring the correct spatial responses. In contrast, rats infused with AP-5 in the nucleus accumbens shell showed little impairment. When rats in all groups had learned the maze and were performing at similar levels, AP-5 had relatively little effect except in the posterior caudate group, where errors and trial times were again increased. These findings demonstrate the importance of NMDA receptor-dependent activity within the accumbens and caudate in spatial learning and performance. The neural processes necessary for adaptive spatial learning in complex environments may recruit multiple cortical systems having specialized functions, which in turn are integrated in widespread striatal regions.
Rats with caudate lesions and pretrained for 36 trials demonstrated impaired performance on the “reference memory” or invariant aspect of a 12-arm radial maze and normal performance on the “working memory” or variable aspect of the maze. Rats with caudate lesions and no pretraining were also impaired on an invariant tactile discrimination in a T maze, but they were not impaired on the variable goal-arm choice of the T maze. More extensive preoperative training ameliorated behavioral deficits of rats with caudate lesions in the T maze and radial arm maze. Results showed that behavioral impairment after damage to the caudate is not restricted to egocentric tasks as previously suggested, but the caudate seems to be involved in the initial acquisition of information that is invariant over many trials.
This study investigated the respective roles of the hippocampus, the amygdala, and the dorsal striatum in learning and memory. A standard set of experimental conditions for studying the effects of lesions to the three brain areas using an 8-arm radial maze was used: a win-shift version, a conditioned cue preference (CCP) version, and a win-stay version. Damage to the hippocampal system impaired acquisition of the win-shift task but not the CCP or win-stay tasks. Damage to the lateral amygdala impaired acquisition of the CCP task but not the win-shift or win-stay tasks. Damage to the dorsal striatum impaired acquisition of the win-stay task but not the win-shift or CCP tasks. These results are consistent with the hypothesis that the mammalian brain may be capable of acquiring different kinds of information with different, more-or-less independent neural systems. A neural system that includes the hippocampus may acquire information about the relationships among stimuli and events. A neural system that includes the amygdala may mediate the rapid acquisition of behaviors based on biologically significant events with affective properties. A neural system that includes the dorsal striatum may mediate the formation of reinforced stimulus-response associations.
Examined the ability of Sprague-Dawley rats to follow different food-searching strategies in a test of spatial memory. In a win–shift procedure, Ss were rewarded for choosing locations different from ones just chosen and in a win–stay procedure, they were rewarded for returning to the locations just chosen. In a 3rd procedure, Ss were rewarded for every choice. The win–shift strategy was learned rapidly and was performed well, whereas the win–stay strategy was learned slowly, if at all. When every choice was rewarded, Ss exhibited a preference for following a win–shift strategy. Data indicate that rats are disposed to follow a win–shift strategy when searching for food. First, they are able to learn a win–shift procedure better than they are able to learn a win–stay procedure. Second, when any choice produces reward, they prefer to follow a win–shift strategy. The influence of this win–shift disposition on food gathering in the wild and on performance of laboratory discrimination tasks is discussed. (25 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The present study examined the effect of lesions of the caudate nucleus or fimbria-fornix on the acquisition of two water maze tasks. In both tasks, two rubber balls with different visual patterns were used as platforms (i.e., cues). The "correct" cue was attached to a submerged rectangular platform and could be mounted by an animal to escape the water. The "incorrect" cue was attached to a thin round pedestal and could not be mounted. In a spatial version of the task, the correct cue was located in the same quadrant of the maze on all trials, whereas the visual pattern on the cue was varied from trial to trial. Lesions of the fornix, but not the caudate nucleus, impaired acquisition of this spatial task in relation to control animals. In a simultaneous visual discrimination version of the task, the correct cue on all trials was one with a specific visual pattern, and the spatial location of the correct cue was varied from trial to trial. Lesions of the caudate nucleus, but not the fornix, impaired acquisition of this visual discrimination task in relation to control animals. The double dissociation observed supports the hypothesis that the hippocampus and caudate nucleus are parts of systems that differ in the type of memory they mediate.
The effect of posttraining intracerebral injections of the indirect dopamine (DA) agonist d-amphetamine, the direct D2 agonist LY 171555, and the direct D1 agonist SKF-38393 on the acquisition of two 8-arm radial maze tasks were examined. On a win-stay task, a light cue signaled the location of food in 4 randomly selected maze arms on each trial, and animals were required to visit each of the lit arms twice within a trial. Posttraining intracaudate injection of d-amphetamine (10.0 and 15.0 micrograms), LY 171555 (2.0 micrograms), and SKF-38393 (5.0 micrograms) all improved win-stay acquisition in relation to saline-injected controls. In contrast, posttraining intrahippocampal injection of DA agonists had no effect on win-stay acquisition. On a win-shift task, rats were allowed to obtain food from 4 randomly selected maze arms, followed by a delay period in which they were removed from the maze. They were returned to the maze for a retention test in which only those arms that had not been visited before the delay contained food. Posttraining intrahippocampal (but not intracaudate) injection of d-amphetamine (5.0 micrograms), LY 171555 (2.0 micrograms), and SKF-38393 (5.0 micrograms) all improved win-shift retention in relation to saline-injected controls. The results demonstrate a double dissociation of hippocampus and caudate nucleus memory functions and show that posttraining injection of both D1 and D2 agonists modulate the memory processes subserved by both hippocampus and caudate nucleus.
Rats with caudate lesions and pretrained for 36 trials demonstrated impaired performance on the "reference memory" or invariant aspect of a 12-arm radial maze and normal performance on the "working memory" or variable aspect of the maze. Rats with caudate lesions and no pretraining were also impaired on an invariant tactile discrimination in a T maze, but they were not impaired on the variable goal-arm choice of the T maze. More extensive preoperative training ameliorated behavioral deficits of rats with caudate lesions in the T maze and radial arm maze. Results showed that behavioral impairment after damage to the caudate is not restricted to egocentric tasks as previously suggested, but the caudate seems to be involved in the initial acquisition of information that is invariant over many trials.
The present experiments were designed to examine the hypothesis that the mammalian brain contains anatomically distinct memory systems. Rats with bilateral lesions of caudate nucleus or fimbria-fornix and a control group were tested postoperatively on 1 of 2 versions of the radial maze task. In a standard win-shift version, each of the 8 arms of the maze was baited once, and the number of errors (revisits) in the first 8 choices of each trial was recorded. Fimbria-fornix rats were impaired in choice accuracy, while caudate animals were unimpaired relative to controls. Different groups of rats with similar lesions were tested on a newly developed win-stay version of the radial maze, in which the location of 4 randomly selected baited arms was signaled by a light at the entrance to each arm, and which required rats to revisit arms in which reinforcement had been previously acquired within a trial. Rats with fimbria-fornix lesions were superior to controls in choice accuracy on the win-stay radial maze task, while caudate animals were impaired relative to controls. The results demonstrate a double dissociation of the mnemonic functions of the hippocampus and caudate nucleus. Some implications of the presence of 2 memory systems in the mammalian brain are discussed.
Reports results of 2 experiments with 27 male Wistar and 27 male hooded Long-Evans rats. Lesions to the medial frontal cortex produced severe deficits on spatial reversal learning and on delayed response, while lesions of the orbital frontal cortex produced perseverative response tendencies on a differential reinforcement of low rates 20-sec schedule and on barpressing extinction. Results are strikingly similar to those resulting from dorsolateral frontal and orbital frontal lesions, respectively, in rhesus monkeys. (24 ref)
Kainic acid (KA) lesions were used to study the effects of damage to the CA3 cell field and subiculum on performance of complex place and cue tasks. In Experiment 1, neuroanatomical techniques were employed to determine the selectivity of the lesions. In a within-subjects design, rats in Experiment 2 were trained before the operations to run on an eight-arm radial maze with procedures that involved two kinds of learning (place and cue) and two memory functions (reference memory and working memory). Interrupting the intrahippocampal circuit by damaging the CA3 cell field with KA had minimal effects on performance; injections into subiculum and complete aspiration lesions of hippocampus resulted in impairments on the place but not the cue task. Only intraventricular injections of KA affected performance on both tasks. These results fail to support either the cognitive map or the working memory theory of hippocampal function. The presence of distant damage beyond the immediate area of injection complicates interpretation of the results and may serve to limit the usefulness of KA as a neurotoxin in behavioral investigations.
Electrophysiological studies have shown that single cells in the
hippocampus respond during spatial learning and
exploration1-4, some firing only when animals enter specific
and restricted areas of a familiar environment. Deficits in spatial
learning and memory are found after lesions of the hippocampus and its
extrinsic fibre connections5,6 following damage to the medial
septal nucleus which successfully disrupts the hippocampal theta
rhythm7, and in senescent rats which also show a correlated
reduction in synaptic enhancement on the perforant path input to the
hippocampus8. We now report, using a novel behavioural
procedure requiring search for a hidden goal, that, in addition to a
spatial discrimination impairment, total hippocampal lesions also cause
a profound and lasting placenavigational impairment that can be
dissociated from correlated motor, motivational and reinforcement
aspects of the procedure.
The emotional reactivity of rats with lesions of the dorsal portion of medial prefrontal cortex (mPFC) was examined using a classical fear conditioning paradigm. Conditioned fear behavior (freezing responses) was measured during both the acquisition and extinction phases of the task. Lesions enhanced fear reactivity to both the conditioned stimulus (CS) and contextual stimuli during both phases, suggesting that dorsal mPFC lesions produce a general increase in fear reactivity in response to fear conditioning. M. A. Morgan, L. M. Romanski, and J. E. LeDoux (1993) found that lesions just ventral to the present lesions had no effect during acquisition of the same task and prolonged the fear response to the CS (but not the context) during extinction. Thus, both dorsal and ventral regions of mPFC are involved in the fear system, but each modulates different aspects of fear responsivity.
Involvement of the hippocampus and caudate nucleus in place and response learning was examined by functionally inactivating these brain regions bilaterally with infusions of lidocaine. Rats were trained to approach a consistently baited arm in a cross-maze from the same start box (four trials/day/14 total days). On Days 8 and 16 a single probe trial was given, in which rats were placed in the start box opposite that used in training and allowed to approach a maze arm. Three minutes prior to the probe trial, rats received bilateral injections of either saline or a 2% lidocaine solution (in order to produce neural inactivation) into either the dorsal hippocampus or dorsolateral caudate nucleus. On the probe trials, rats which entered the baited maze arm (i.e., approached the place where food was located during training) were designated place learners, and rats which entered the unbaited maze arm (i.e., made the same turning response as during training) were designated response learners. Saline-treated rats displayed place learning on the Day 8 probe trial and response learning on the Day 16 probe trial, indicating that with extended training there is a shift in learning mechanisms controlling behavior. Rats given lidocaine injections into the hippocampus showed no preference for place or response learning on the Day 8 probe trial, but displayed response learning on the Day 16 probe trial, indicating a blockade of place learning following inactivation of the hippocampus. Rats given lidocaine injections into the caudate nucleus displayed place learning on both the Day 8 and the Day 16 probe trials, indicating a blockade of response learning following inactivation of the caudate nucleus. The findings indicate: (1) the hippocampus and caudate nucleus selectively mediate expression of place and response learning, respectively (2), in a visually cued extramaze environment, hippocampal-dependent place learning is acquired faster than caudate-dependent response learning, and (3) when animals shift to caudate-dependent response learning with extended training, the hippocampal-based place representation remains intact.
Two experiments were conducted to compare the effects of fornix/fimbria and caudate-putamen lesions in Long-Evans hooded rats (Rattus norvegicus) trained on two water maze tasks that differed in the type of spatial localization required for optimum solution. In Experiment 1, the lesioned rats and surgical controls were trained on the standard place task in the water maze (Morris, 1981) and given two postacquisition tests (a platform removal probe and platform relocation test). In Experiment 2, rats with similar lesions and control rats were trained on a modified cue navigation task. Fornix/fimbria lesions impaired a late stage of place task acquisition but did not impair acquisition of the cue task. Caudate-putamen lesions resulted in a severe place acquisition impairment and a transient cue acquisition impairment, both of which were characterized by an initial tendency to swim near the wall of the pool. Post-hoc analyses of the direction and angles of departure from the start points suggested that rats with fornix/fimbria lesions used non-allocentric spatial strategies to solve the place task. These rats also demonstrated a significantly weakened spatial bias for the former training quadrant on the platform removal probe and reduced flexibility in navigating to a novel platform location on the platform relocation test. In contrast, rats with caudate-putamen lesions showed a significant spatial bias for the former training quadrant but failed to cross the exact location within the quadrant where the platform was formerly positioned. The results suggest that the hippocampus mediates the allocentric spatial component of the water maze place task while the dorsomedial striatum may play an important role in the acquisition of the procedural aspects of both place and cue versions of the task.
Rats received an 8-trial training session on a spatial or cued task in a water maze, followed by a posttraining intracerebral injection of AP5 or saline. On a retention test 24 hr later, latency to mount the escape platform was used as a measure of memory. Intrahippocampal (10 micrograms), but not intra-dorsal striatal (2, 5, or 10 micrograms), injection of AP5 impaired memory in the spatial task. In contrast, intra-dorsal striatal (2 micrograms), but not intrahippocampal (2, 5, or 10 micrograms) injection of AP5 impaired memory in the cued task. Intracerebral injections of AP5 delayed 2 hr posttraining were ineffective. The findings indicate a double dissociation of the roles of the hippocampus and dorsal striatum in memory, a role for N-methyl-D-aspartate receptor function in posttraining memory processes, and a glutamatergic modulation of both hippocampal and dorsal striatal memory processes, suggesting that different forms of memory may share a similar neurochemical basis.
We investigated the effects of localized medial and lateral CPu lesions and fornix/fimbria lesions on responses to a local cue and to behavior based on cognitive-spatial information in the water maze. Rats were trained concurrently on the cue (visible platform) and spatial (submerged platform) components of the task, followed by a test in which responses to the two types of information were dissociated by a measure of competing response tendencies. Bilateral lesions of lateral CPu did not affect acquisition of either cue or spatial responding but produced a preference for the spatial response on the competition test. Bilateral lesions of the medial CPu retarded but did not prevent learning both components and produced a preference for the cue response on the competition test. The latter effect was accompanied by increased thigmotaxis (swimming in the periphery of the pool), primarily during the early acquisition trials, which was attributed to an impaired ability to respond to learned spatial information. Fornix/fimbria lesions prevented spatial but not cue learning and produced a preference for the cue response on the competition test. Asymmetric lesions (unilateral hippocampus and contralateral medial CPu) produced mild retardation of acquisition of both the cue and spatial tasks and a preference for the cue response on the competition test. These findings dissociate the functions of the lateral and medial CPu and suggest that the hippocampus and medial CPu may be parts of a system that promotes responding based on learned cognitive-spatial information, particularly in competitive cue-place response situations.
Rats with dorsomedial or dorsolateral caudate-putamen lesions and sham-operated controls were trained on the standard hidden platform (place) task in the water maze. Compared to controls, rats with dorsomedial, but not dorsolateral lesions were slower to escape to the hidden platform and spent significantly more time swimming near the wall of the pool (thigmotaxis) on the early trials, but eventually achieved control levels of performance. When the platform was removed from the pool, all groups exhibited a significant bias for swimming in the training quadrant and crossing the former location of the platform. In the second phase of the experiment rats were given visible platform (cue) training in a different room/pool with the platform moved to a new location each day. Rats with dorsomedial, but not dorsolateral lesions required more trials to reach criterion; again, thigmotaxis was observed on the early trials. The third phase, carried out in the original room/pool, included a place-retention trial followed by a place-cue competition test, (i.e. a choice between the learned spatial location of the hidden platform and the visible platform in a new location). The rats with dorsomedial, but not dorsolateral lesions swam to the visible platform more frequently than the controls. In the final phase, the rats in both lesion groups exhibited slightly lower thigmotactic tendencies than controls in a standard dry-land open field, a finding inconsistent with the hypothesis that thigmotaxis in the water maze is due to increased fear or anxiety. Taken together with other behavioral and anatomical findings, the results suggest that the dorsomedial caudate-putamen, by virtue of its connections with limbic and prefrontal cortical regions, may mediate a response selection process that integrates cognitive information with stimulus-response tendencies.
In order to examine the role of the hippocampus in spatial learning, fimbria-fornix-lesioned (FF) rats and control rats were trained in a water maze enclosed in black curtains. In the condition with stimuli, two objects of different appearance were hung on the water surface as intramaze stimuli. The hidden goal and two objects formed a triangle, and their spatial relationship was kept constant throughout the training. For the condition without stimuli, the two stimuli were removed. In the condition with stimuli, the control group solved the task faster than the FF group. Analysis of navigational strategy indicated that the control group used both the place strategy and the response strategy, whereas the FF group used only the response strategy. In the condition without stimuli, the performance of both groups was similar, with both groups solving the task using only the response strategy. These results suggest that the hippocampus plays an important role in utilization of the spatial relationships among intramaze stimuli.
Rats with hippocampal lesions (n = 16), sham-operated controls (n = 5), and unoperated controls (n = 8) were trained on place and cue tasks in an elevated radial arm maze. Hippocampallesioned rats had impaired working memory and impaired cognitive-map formation. The behavior of the hippocampals in choosing arms was different from that of the controls even immediately after training began. The hippocampals were not able to rapidly perceive the spatial requirements of the task and did not show the inherent stereotyped behavior employed by controls. Nonetheless, the hippocampals showed that they could learn problem-solving behavior as training progresses.
Win-shift spatial memory tasks in a radial maze reinforce animals for avoiding previously visited rewarded arms; win-stay tasks reinforce them for returning to those arms. Win-shift tasks have generally been found much easier to perform, and this may be explained either in terms of foraging models which postulate avoidance of locations where food has been found, or in terms of the predominance of spontaneous alternation (exploration). Experiment 1 examined spontaneous alternation behavior in the radial maze as a function of whether the first visit to an arm had been rewarded or not, and showed that alternation was more probable after nonreward than after reward in both hungry and thirsty rats (a result which conflicts with the foraging account of the win-shift superiority). Experiment 2 replicated the finding that win-stay discrimination performance was inferior to win-shift. A manipulation (lengthening the delay between initial and test choices) which weakens spontaneous alternation, reduced, but did not reverse, the win-shift superiority. In Experiment 3, in order to eliminate the influence of spontaneous alternation, versions of the win-stay and win-shift tasks were devised in which, unlike the original task, all arms were familiar at the choice trial. Under those conditions win-stay was performed better than win-shift. It is concluded that spontaneous alternation plays a major role in many spatial memory tasks, and that the results can best be accounted for by combining principles of exploration and simple associative learning, without recourse to foraging models.
Recent data have emphasized the neurochemically distinct nature of subterritories in the accumbens part of the rat ventral striatum termed the core, shell, and rostral pole. In order to gain a more comprehensive understanding of how afferents are distributed relative to these subterritories, immunohistochemical detection of retrogradely transported Fluoro-Gold was carried out following iontophoretic injections intended to involve selectively one of the subterritories. The data revealed that a number of cortical afferents of the medial shell and core originate in separate areas, i.e., the dorsal peduncular, infralimbic, and posterior piriform cortices (to medial shell) and the dorsal prelimbic, anterior agranular insular, anterior cingulate, and perirhinal cortices (to core). The lateral shell and rostral pole are innervated by cortical structures that also project either to the medial shell or core. The orbital, posterior agranular insular, and entorhinal cortices, hippocampus, and basal amygdala were observed to innervate the accumbens in a topographic manner. Following core injections, strong bilateral cortical labeling was observed. Few labeled cortical cells were observed contralaterally following injections in the medial shell. Intermediate numbers of labeled neurons were observed in contralateral cortices following lateral shell injections.
Robust subcortical labeling in a variety of structures in the ventral forebrain, lateral hypothalamus, deep temporal lobe, and brainstem was observed after shell injections, particularly those that involved the caudal dorsomedial extremity of the shell, i.e., its “septal pole.” Selective ipsilateral labeling of subcortical structures in the basal ganglia circuitry was observed following injections in the core and, to a lesser extent, lateral shell.
It was concluded that a number of afferent systems exhibit varying degrees of segregation with respect to the accumbal subterritories.
Using the Morris swimming pool test of spatial navigation, medial caudate-putamen lesions in rats produce impairments in the acquisition and retention of both place and cue tasks, and impair the selection of normal navigation strategies. Also described are some novel features of spatial navigation behaviour displayed by control animals in cue and place tasks that provide insights into the performance of the caudate-putamen rats. Analyses of the swim patterns on postacquisition probe trials, in which the target platform was removed or relocated, showed that the strategy used by the caudate-putamen lesioned rats was dependent upon the task that they were required to solve. Control rats used a place strategy and distal visual cues to identify the location of the start points, the routes from the start points to the platform, and the location of the platform on both the cue and place tasks. The caudate-putamen lesioned rats used distal visual cues and a place strategy only to acquire the place task. They solved the cue task using a taxon strategy consisting of a combination of proximal and position response cues. The results suggest that when necessary, medial caudate-putamen lesioned rats, like normal rats, can use place strategies for spatial navigation, but if an alternate, perhaps simpler, taxon solution is available they seemingly ignore place information and navigate using the simpler strategy. The deficit, which has features of a neglect rather than a loss of ability per se, suggests that medial caudate-putamen neural systems are involved in the selection of alternative strategies in spatial navigation tasks.
The behavior of rats with chronic lesions of the head of the caudate-putamen or of the dorsomedial nucleus of the thalamus was examined in a variety of situations known to be sensitive to damage to the medial prefrontal or orbital prefrontal cortex of rats, respectively. Lesions of either structure produced behavioral changes that were similar to those previously observed following prefrontal removals. These changes included decreased food hoarding, altered social behavior, impaired learning of spatial reversals and increased resistance to extinction. The similarity in the effects of prefrontal, caudate, and dorsomedial thalamic lesions suggest that these structures are components of the same functional system(s).
Groups of Long-Evans rats with bilateral lesions of the caudate nucleus, sham lesions, or no lesions were given one trial per day in an eight-arm radial maze. The same four maze arms were baited on each trial. The remaining four arms never contained food. Optimal performance required animals to enter each of the baited arms only once on each trial and to avoid entering the arms in the unbaited set. Rats with caudate lesions learned to enter each of the baited arms only once on each trial. However, these rats were severely impaired in learning to avoid entering the arms in the unbaited set. Implications for dual-memory theories are discussed.
Rats with ibotenate lesions of either the medial striatum or the lateral striatum were trained in a forelimb reaching task and in acquisition, retention and reversal of either turn (left-right) discrimination or brightness (black-white) discrimination in a cross-shape maze. Compared with the controls, the rats with lesions of the medial striatum showed a reliable, modality-selective impairment in reversal of turn discrimination, but no significant impairment of reaching. In contrast, the rats with lateral striatal lesions showed a significant impairment of forelimb reaching, but not of reversal of either discriminations. Neither medial nor lateral lesions significantly affected acquisition and retention of both discriminations. The findings indicate a predominant role of the medial striatum in monitoring of directional responses, confirm the regionally specific role of the lateral striatum in reaching, and are interpreted to support the hypothesis of parallel motor and cognitive forebrain circuits comprising distinctive regions of the striatum.
The detailed organization of the corticostriate projection has been investigated in the brain of the rat using the technique of retrograde transport of horseradish peroxidase following the placement of small, iontophoretic injections of horseradish peroxidase conjugated to lectin throughout all major regions of the striatum (caudate-putamen, nucleus accumbens and olfactory tubercle). The results demonstrate that all major regions of the cerebral cortex project to the striatum on both sides of the brain with an ipsilateral predominance. The cells of origin of both the ipsilateral and contralateral corticostriate projections lie mainly in lamina V (especially lamina Va) with very small numbers in lamina III of the neocortex and mesocortex, and in the deep laminae of the allocortex. The results show that each striatal locus receives inputs from several cortical regions, i.e. there is extensive overlap in the corticostriate projection, and that, in general terms, each cortical region projects onto a longitudinally oriented region of the striatum. In particular, the major subdivisions of the cerebral cortex--the neocortex, mesocortex and allocortex--project onto defined but partially overlapping regions of the striatum: the neocortex projects to the caudate-putamen; the mesocortex projects mainly to the medial and ventral regions of the caudate-putamen but also to the ventral striatum (nucleus accumens and olfactory tubercle); and the allocortex projects mainly to the ventral striatum but also to the medial and ventral parts of the caudate-putamen. Within each of these major projection systems there is a further organization, with the constituent parts of each major cortical region projecting to smaller longitudinal components of the major projection fields. Each neocortical area projects to a longitudinal region of the dorsal striatum (caudate-putamen): the sensory and motor areas project topographically onto the dorsolateral striatum such that the rostral sensorimotor cortex (head areas) projects to central and ventral regions and the more caudal sensorimotor cortex (limb areas) projects to dorsal regions of the dorsolateral striatum; the visual area projects to the dorsomedial striatum; and the auditory area projects to the medial striatum. Each mesocortical area projects to a longitudinal area of the striatum: the most posteromedial mesocortex (the retrosplenial area) projects to the dorsomedial striatum; more anterior and lateral parts of the mesocortex project to more ventral parts of the striatum: and the most lateral mesocortex (the agranular insular and perirhinal areas) project to the ventrolateral striatum.(ABSTRACT TRUNCATED AT 400 WORDS)
Ablation of the newly described cortical projection area of the dorsomedial thalamic nucleus impaired spatial reversal retention; ablation of the frontal poles did not. Caudate lesions produced an even stronger reversal deficit. These data extend comparability of effects of prefrontal ablations to the rat and permit the inference of the existence of the system in this species. frontal lobeRésuméL'ablation des projections corticales, nouvellement décrites, du noyau thalamique dorso-médian perturbe la rétention du renversement spatial tandis que l'ablation des pôles frontaux ne le fait pas. Les lésions caudées produisent un déficit dans ces épreuves de renversement encore plus accusé. Ces données permettent de comparer les effets des ablations préfontales obtenues chez le rat à ceux obtenués chez les carnivores et les primates. On peut aussi en déduire l'existence d'un systeme du lobe frontal chez le rat.ZusammenfassungDie Abtragung der kürzlich beschriebenen corticalen Projektion des dorsomedialen Thalamuskernes führt zu einer Beeinträchtigung der räumlichen Umkehr, die Entfernung des Frontalpoles dagegen nicht. Caudatumläsionen verursachen ein stärkeres Umkehrdefizit. Diese Ergebnisse erlauben, Wirkungen von praefrontalen Abtragungen bei Ratten zu vergleichen und zeigen, daβ bei dieser Spezies ein Frontallappensystem vorhanden ist.
Rats with lesions of the medial frontal cortex or dorsomedial nucleus of the thalamus (MD) were studied in two spatial localization tasks: the Morris water task and the 8-arm radial arm maze. Rats with medial frontal lesions failed to learn to swim from different locations to a hidden platform located at a specific place in a large tank (Morris task) and were impaired at learning the location of reward in the radial arm maze. Rats with MD lesions were not impaired at spatial orientation in either task. The results provide the first unequivocal evidence of a spatial orientation deficit following frontal lesions and lend support to the notion that the frontal cortex forms part of a 'spatial mapping system'. The results suggest that although MD is the major afferent to the frontal cortex, it does not provide necessary spatially-relevant input.
The effect of ventral medial frontal cortex (MFC) lesions on heart rate and blood pressure during conditioned emotional responses (CER) was investigated. Male Sprague-Dawley rats were divided into two groups: MFC-lesioned rats (n = 11) sustained bilateral lesions of the infralimbic and ventral prelimbic regions of the MFC via microinjection of the neurotoxin N-methyl-D-aspartate; Controls (n = 13) received sterile saline. Following a 2-week recovery period, all animals were trained; one of two tones served as the conditioned stimulus (CS) and a 2 mA footshock served as the unconditioned stimulus (US). The CS+ tone was consistently paired with the US, while the CS- tone was randomly paired with the US. Heart rate and blood pressure were recorded during CS+ and CS- presentations before and after administration of the following pharmacological agents: atropine, atenolol, and atropine + atenolol. All animals responded to the CS+ with increased BP compared to baseline; the increase was not significantly different between groups. Controls responded to the CS+ with increased HR, while MFC-lesioned animals displayed a bimodal HR response which was not significantly different from baseline, but was significantly different from Controls. Pharmacological blockade of the HR response revealed coactivation of the sympathetic and parasympathetic nervous systems during the CS+, with a significant decrease (52%) in the sympathetic tachycardia component of the CS+ HR response in MFC-lesioned rats as compared to Controls; the parasympathetic bradycardia component was not altered by MFC lesions. In all cases, CS- responses were smaller than the CS+ responses. Pharmacological analysis revealed that the CS- HR response was mediated by the sympathetic component only, which was also significantly reduced in MFC-lesioned animals as compared to Controls. This significant reduction in the sympathetically mediated HR component of both the reinforced CER (CS+) and the unreinforced CER (CS-) following ventral MFC lesions implies that the MFC is necessary for complete sympathetic activation of cardiovascular responses to both severely and mildly stressful stimuli. The role of the MFC in emotion is also discussed.
This experiment investigated the ability of rats with dorsal striatal or fornix damage to learn the location of a visible platform in a water maze. We also assessed the animals' ability to find the platform when it was hidden (submerged). Rats with neurotoxic damage to the dorsal striatum acquired both the visible and hidden platform versions of the task, but when required to choose between the spatial location they had learned and the visible platform in a new location they swam first to the old spatial location. Rats with radio-frequency damage to the fornix acquired the visible platform version of the water maze task but failed to learn about the platform's location in space. When the visible platform was moved to a new location they swam directly to it. Normal rats acquired both the visible and hidden platform versions of the task. These findings suggest that in the absence of a functional neural system that includes dorsal striatum, spatial information predominantly controlled behavior even in the presence of a cue that the animals had previously been reinforced for approaching. In the absence of a functional hippocampal system behavior was not affected by spatial information and responding to local reinforced cues was enhanced. The results support the idea that different neural substrates in the mammalian nervous system acquire different types of information simultaneously and in parallel.
Based on behavioral procedures aimed at measuring working or data-based memory for spatial location, response, and visual object information, it is shown that there is a triple dissociation among the hippocampus, caudate nucleus, and extrastriate visual cortex in mediating spatial location, response, and visual object information, respectively. The hippocampus appears to subserve only spatial location, the caudate nucleus only response, and the extrastriate visual cortex only visual object information. The results support the neurobiological foundation of the attribute memory model.
Huntington's disease (HD) in an inherited neurodegenerative disorder in which the striatum undergoes marked atrophic changes. Patients with HD typically have impaired cognitive function, including deficient visuospatial skills, lack of cognitive flexibility and poor recall of memories. The relationship between these cognitive abnormalities and the striatal degeneration of HD is incompletely understood. In order to explore this issue, we studied the behavior of rats with histologically confirmed bilateral quinolinate (QUIN)-induced lesions of the medial striatum. In a series of Morris Water Maze (MWM) experiments and Delayed Alternation (DA) tests, QUIN-lesioned animals exhibited: (i) impaired acquisition of visuospatial skills; (ii) impaired "transfer of learning"; (iii) preseverative behavior; (iv) deficient retrieval or retention of stored memories. The lesioned rats were unimpaired with swimming to a visible platform, while moving spontaneously in behavior boxes, and when performing various specialized tests of motor function. These results indicate that QUIN-induced lesions of the medial striatum can produce impairments of visuospatial skills, cognitive flexibility, and recall. These are the categories of cognitive function that are disturbed in HD. This suggests that the striatal degeneration of HD could be a sufficient explanation for the cognitive abnormalities associated with the illness.
In rats, hippocampal lesions result in impairment of spatial navigation, although other learning abilities remain unaltered. When learning a left/right discrimination task, rats can use a spatial strategy (with external maze landmarks-Situation 1) or are forced to use an egocentric strategy (without external or internal maze cues-Situation 2). Little is known about the extrahippocampal systems involved in the utilization of egocentric strategy. It is suggested that striatum could play an important role in the learning abilities that are spared after hippocampal lesion. The aim of our study was to investigate which strategy is used by rats bearing hippocampal or caudate-putamen lesions in the acquisition of a left/right discrimination task in an elevated T-maze in both Situations 1 and 2. We also investigated the effect of each lesion on the reversal of discrimination in both situations. Acquisition was not altered in any of the situations; however, a transfer test showed that hippocampal-lesioned rats used a different strategy (egocentric) from control animals (spatial) in Situation 1. In addition, reversal of the discrimination was impaired in Situation 2. Caudate-putamen lesion produced a transient effect on reversal of discrimination only in the egocentric task (Situation 2), but did not impair acquisition of the task in either situation, thus suggesting that the animals were able to use either strategy.
These experiments addressed the role of striatal N-methyl-D-aspartate (NMDA) receptors in spatial behavior in the radial arm maze. Rats treated with the NMDA antagonist D-2-amino-5-phosphonopentanoic acid (AP-5) in the nucleus accumbens core, medial caudate, and posterior caudate were all significantly impaired in acquiring the correct spatial responses. In contrast, rats infused with AP-5 in the nucleus accumbens shell showed little impairment. When rats in all groups had learned the maze and were performing at similar levels, AP-5 had relatively little effect except in the posterior caudate group, where errors and trial times were again increased. These findings demonstrate the importance of NMDA receptor-dependent activity within the accumbens and caudate in spatial learning and performance. The neural processes necessary for adaptive spatial learning in complex environments may recruit multiple cortical systems having specialized functions, which in turn are integrated in widespread striatal regions.
Frontal lobe system and spatial reversal in the rat
- Divac
Impairments in the acquisition, retention and selection of spatial navigation strategies after medial caudate-putamen lesions in rats
- Whishaw