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![Anatomical localization of caudal dentate nucleus (DN) recordings. A: example MRI section of monkey R (coronal slice, left hemisphere). A temporarily implanted reference electrode was aimed at the electrophysiologically identified left DN, but positioned with its tip several millimeters above recording sites to prevent damage during the MRI procedure. Shadow tracks in the MRI (medial to reference electrode) are from exploratory electrode penetrations. B: electrode paths reproduced from coronal (left) and parasagittal (right) MRI sections, reproduced onto scaled excerpts of atlas sections from http://brainmaps.org/ajaxviewer.php?datid3&sname0394 [from Mikula et al. 2008], showing intersection of trajectory with ventral-caudal DN. C: histology from monkey F, showing cerebellar sections 250 m apart from rostral (top) to caudal (bottom). Top: in this section, 10 mm posterior to the interaural line ("P10"), the DN and the interpositus nucleus (IN) are visible, both outlined for clarity. Middle: slightly more posterior, the caudal pole of the DN is visible (outlined), as well as gliosis above it from repeated electrode penetrations into it. Bottom: one more section posterior to that, the DN is not present any more.](profile/Marc-Sommer-2/publication/235386328/figure/fig2/AS:667636304187394@1536188307242/Anatomical-localization-of-caudal-dentate-nucleus-DN-recordings-A-example-MRI-section.png)
Anatomical localization of caudal dentate nucleus (DN) recordings. A: example MRI section of monkey R (coronal slice, left hemisphere). A temporarily implanted reference electrode was aimed at the electrophysiologically identified left DN, but positioned with its tip several millimeters above recording sites to prevent damage during the MRI procedure. Shadow tracks in the MRI (medial to reference electrode) are from exploratory electrode penetrations. B: electrode paths reproduced from coronal (left) and parasagittal (right) MRI sections, reproduced onto scaled excerpts of atlas sections from http://brainmaps.org/ajaxviewer.php?datid3&sname0394 [from Mikula et al. 2008], showing intersection of trajectory with ventral-caudal DN. C: histology from monkey F, showing cerebellar sections 250 m apart from rostral (top) to caudal (bottom). Top: in this section, 10 mm posterior to the interaural line ("P10"), the DN and the interpositus nucleus (IN) are visible, both outlined for clarity. Middle: slightly more posterior, the caudal pole of the DN is visible (outlined), as well as gliosis above it from repeated electrode penetrations into it. Bottom: one more section posterior to that, the DN is not present any more.
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The caudal dentate nucleus (DN) in lateral cerebellum is connected with two visual/oculomotor areas of the cerebrum, the frontal eye field (FEF) and lateral intraparietal (LIP) cortex. Many neurons in FEF and LIP produce "delay activity" between stimulus and response that correlates with processes such as motor planning. Our hypothesis was that cau...
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... lateral cerebellar cortex and deep nuclei, with a focus on the DN. Each DN was mapped extensively with recordings to determine its caudal and lateral borders (6 -7 mm lateral from the midline), and its location was verified by structural MRI with implanted electrodes for reference. An example magnetic resonance image from monkey "R" is shown in Fig. 1A along with matching, scaled atlas illustrations for reference ( Fig. 1B; Mikula et al. 2008). At the conclusion of experiments, we additionally confirmed the caudal DN recording locations histologically in monkey "F" (Fig. 1C, details in Histology below). During recording sessions, we could readily distinguish the DN from cerebellar ...
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... DN was mapped extensively with recordings to determine its caudal and lateral borders (6 -7 mm lateral from the midline), and its location was verified by structural MRI with implanted electrodes for reference. An example magnetic resonance image from monkey "R" is shown in Fig. 1A along with matching, scaled atlas illustrations for reference ( Fig. 1B; Mikula et al. 2008). At the conclusion of experiments, we additionally confirmed the caudal DN recording locations histologically in monkey "F" (Fig. 1C, details in Histology below). During recording sessions, we could readily distinguish the DN from cerebellar cortex on the basis of 1) depth referenced to MRI measurements; 2) ...
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... by structural MRI with implanted electrodes for reference. An example magnetic resonance image from monkey "R" is shown in Fig. 1A along with matching, scaled atlas illustrations for reference ( Fig. 1B; Mikula et al. 2008). At the conclusion of experiments, we additionally confirmed the caudal DN recording locations histologically in monkey "F" (Fig. 1C, details in Histology below). During recording sessions, we could readily distinguish the DN from cerebellar cortex on the basis of 1) depth referenced to MRI measurements; 2) surrounding regions of white matter as evidenced by little neuronal activity; 3) complex spikes above, and depending on location, below the white matter; and 4) ...
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... recorded from 79 neurons in the caudal pole of DN (Fig. 1). The sample included 49 neurons from monkey F (23 neurons from the left DN plus 26 neurons from the right DN) and 30 neurons from monkey R (all from the left DN). The most striking characteristic of the neurons was their prominent delay activity, which spanned long periods of time leading up to movement initiation. Figure 3 shows ...
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... profiles that they observed resembled time-com- pressed versions of the activity patterns we found: high base- line firing rates, often a pause just after a sensory cue, and often quick but smooth ramps up and/or down during the movement. Their movement-related activity often had peaks or troughs that correlated with movement initiation (their Figs. 6 -10) and often had directional selectivity (their Fig. 8). They encoun- tered eye movement-related neurons, notably in the caudal one-third of the DN, but did not study them. Fig. 9. Example of a short-lead burster (SLB) neuron recorded more rostral to the other neurons of our study. A: the neuron's activity during the VS task was ...
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Neurophysiological studies of decision making have primarily focused on decisions about information that is stable over time. However, during natural behavior, animals make decisions in a constantly changing environment. To investigate the neural mechanisms of such dynamic choices, we recorded activity in dorsal premotor (PMd) and primary motor cor...
Citations
... Human functional imaging studies using a similar task have reported increased regional blood flow in the cerebellar crus I during predictive (synchronized) saccades compared to reactive saccades 40 . We examined single neuron activity during synchronized saccades from the posterior portion of the cerebellar dentate nucleus, which receives input from the lateral lobules of the cerebellum and is involved in self-initiated eye movements 41,42 . We found that many neurons exhibited activity correlated with saccade timing and temporal errors, and some responded to eye movements in both directions with enhanced activity during predictive synchronized saccades. ...
Movements synchronized with external rhythms are ubiquitous in our daily lives. Despite the involvement of the cerebellum, the underlying mechanism remains unclear. In monkeys performing synchronized saccades to periodically alternating visual stimuli, we found that neuronal activity in the cerebellar dentate nucleus correlated with the timing of the next saccade and the current temporal error. One-third of the neurons were active regardless of saccade direction and showed greater activity for synchronized than for reactive saccades. During the transition from reactive to predictive saccades in each trial, the activity of these neurons coincided with target onset, representing an internal model of rhythmic structure rather than a specific motor command. The behavioural changes induced by electrical stimulation were explained by activating different groups of neurons at various strengths, suggesting that the lateral cerebellum contains multiple functional modules for the acquisition of internal rhythms, predictive motor control, and error detection during synchronized movements. It remains unclear how the brain represents information regarding synchronized movements. Here, the authors investigated the response properties of cerebellar cells in macaques performing a synchronized saccade task and found three groups of cerebellar neurons with distinct peri-saccade response profiles.
... Given its reciprocal connections with the relevant neocortical regions (Kelly and Strick, 2003), the cerebellum may form an additional hub in this voluntary motor control circuitry (Tanaka et al., 2003;Peterburs et al., 2012;Brunamonti et al., 2014;Kunimatsu et al., 2016;Dacre et al., 2021). This possibility is supported by recent findings that the cerebellum participates in movement planning (Ashmore and Sommer, 2013;Giovannucci et al., 2017;Deverett et al., 2018;Gao et al., 2018;Kostadinov et al., 2019). However, to what extent different parts of the cerebellum contribute to the planning and execution of antisaccades, and complex movements in general, is unclear (Miall et al., 1993;Thach, 2007;Ito, 2008;Gao et al., 2018;Chabrol et al., 2019;De Schutter, 2019). ...
... The current data are compatible with the possibility that modules in the medial regions of the oculomotor cerebellum contribute mainly, but not exclusively, to the fine control of saccade dynamics and endpoints (Robinson and Fuchs, 2001;Thier et al., 2002;Herzfeld et al., 2015;Soetedjo et al., 2019), while the lateral cerebellum may be more concerned with higher cognitive functions, such as preparatory processes that occur early after the stimulus onset (Chabrol et al., 2019). Indeed, the lateral regions of the cerebellum appear well connected to neocortical regions that contribute to complex forms of error detection and behavioral adjustment, and they can show activity changes that also correlate with events before the movement execution (Mano et al., 1991;Ashmore and Sommer, 2013;Kunimatsu et al., 2016). ...
... The main target of PC microzones in the lateral cerebellum is the dentate nucleus (Chabrol et al., 2019). Similar to the neurons in the interposed nucleus that are involved in eyeblink conditioning (Ten Brinke et al., 2017), the neurons in the dentate nucleus that are involved in saccade-related behavior can show increases and decreases (Ashmore and Sommer, 2013;Kunimatsu et al., 2018). Kunimatsu et al. (2018) found only upward modulating units during self-initiated saccades, but Ashmore and Sommer (2013) revealed groups of both facilitation and suppression cells during delayed saccades. ...
Volitional suppression of responses to distracting external stimuli enables us to achieve our goals. This volitional inhibition of a specific behavior is supposed to be mainly mediated by the cerebral cortex. However, recent evidence supports the involvement of the cerebellum in this process. It is currently not known whether different parts of the cerebellar cortex play differential or synergistic roles in the planning and execution of this behavior. Here, we measured Purkinje cell (PC) responses in the medial and lateral cerebellum in two rhesus macaques during pro- and anti-saccade tasks. During an antisaccade trial, non-human primates (NHPs) were instructed to make a saccadic eye movement away from a target, rather than toward it, as in prosaccade trials. Our data show that the cerebellum plays an important role not only during the execution of the saccades but also during the volitional inhibition of eye movements toward the target. Simple spike (SS) modulation during the instruction and execution periods of pro- and anti-saccades was prominent in PCs of both the medial and lateral cerebellum. However, only the SS activity in the lateral cerebellar cortex contained information about stimulus identity and showed a strong reciprocal interaction with complex spikes (CSs). Moreover, the SS activity of different PC groups modulated bidirectionally in both of regions, but the PCs that showed facilitating and suppressive activity were predominantly associated with instruction and execution, respectively. These findings show that different cerebellar regions and PC groups contribute to goal-directed behavior and volitional inhibition, but with different propensities, highlighting the rich repertoire of the cerebellar control in executive functions.
... As such, saccade latency, which is the duration that it takes for the eye to initiate a movement towards the target, is controlled by central and cortical structures, while speed of eye movement and accuracy, i.e. how fast and how well the eyes land on the target, are controlled by both cortical and premotor structures at the brainstem level where the motor command is initiated [2]. The speed and amplitude of the saccades may involve the saccade burst generator located in the paramedian pontine reticular formation in the brainstem, which receives direct and/or indirect input from cortical structures (e.g., frontal eye field, parietal cortex), superior colliculus, and cerebellum [50,51]. Thus, our results, by providing detailed normative data for different components of eye (and/or hand) movements, may constitute the basis for understanding and evaluating disturbances of many neural pathways as a result of various neurological conditions. ...
Eye movements measured by high precision eye-tracking technology represent a sensitive, objective, and non-invasive method to probe functional neural pathways. Oculomotor tests (e.g., saccades and smooth pursuit), tests that involve cognitive processing (e.g., antisaccade and predictive saccade), and reaction time tests have increasingly been showing utility in the diagnosis and monitoring of mild traumatic brain injury (mTBI) in research settings. Currently, the adoption of these tests into clinical practice is hampered by a lack of a normative data set. The goal of this study was to construct a normative database to be used as a reference for comparing patients’ results. Oculomotor, cognitive, and reaction time tests were administered to male and female volunteers, aged 18–45, who were free of any neurological, vestibular disorders, or other head injuries. Tests were delivered using either a rotatory chair equipped with video-oculography goggles (VOG) or a portable virtual reality-like VOG goggle device with incorporated infrared eye-tracking technology. Statistical analysis revealed no effects of age on test metrics when participant data were divided into pediatric (i.e.,18–21 years, following FDA criteria) and adult (i.e., 21–45 years) groups. Gender (self-reported) had an effect on auditory reaction time, with males being faster than females. Pooled data were used to construct a normative database using 95% reference intervals (RI) with 90% confidence intervals on the upper and lower limits of the RI. The availability of these RIs readily allows clinicians to identify specific metrics that are deficient, therefore aiding in rapid triage, informing and monitoring treatment and/or rehabilitation protocols, and aiding in the return to duty/activity decision. This database is FDA cleared for use in clinical practice (K192186).
... Although ramping activity is present on cortical, collicular, and tectal neurons ahead of spontaneous saccades, removal of these regions does not alter spontaneous saccade performance and apparently timing in the dark [23][24][25] . This suggests that structures in the hindbrain could be involved in the initiation of spontaneous saccades, an obvious choice being the pons, but potentially as well the cerebellum, where recently neurons associated with self-timing of saccades to visual targets have been found 26 . ...
Organisms have the capacity to make decisions based solely on internal drives. However, it is unclear how neural circuits form decisions in the absence of sensory stimuli. Here we provide a comprehensive map of the activity patterns underlying the generation of saccades made in the absence of visual stimuli. We perform calcium imaging in the larval zebrafish to discover a range of responses surrounding spontaneous saccades, from cells that display tonic discharge only during fixations to neurons whose activity rises in advance of saccades by multiple seconds. When we lesion cells in these populations we find that ablation of neurons with pre-saccadic rise delays saccade initiation. We analyze spontaneous saccade initiation using a ramp-to-threshold model and are able to predict the times of upcoming saccades using pre-saccadic activity. These findings suggest that ramping of neuronal activity to a bound is a critical component of self-initiated saccadic movements.
... Concernant le rôle de ce noyau dans l'oculomotricité de façon large, nous pouvons souligner qu'il reçoit des afférences du NRTP et projette vers plusieurs centres oculomoteurs tels que la PPRF et le noyau interstitiel de Cajal ou même vers les motoneurones du muscle droit latéral par une voie tri-synaptique (Prevosto et al., 2017). Les neurones du noyau dentelé contenus dans sa partie caudale sont caractérisés par une activité similaire à celle des LLBNs liée à la préparation des saccades oculaires (Ashmore & Sommer, 2013;Hepp et al., 1982) et à la prédiction d'événements sensoriels (Ohmae et al., 2013). Parallèlement, certains neurones localisés dans sa partie rostrale présentent une activité de type SLBN qui précède le début du mouvement (W. A. MacKay, 1988), ce qui suggère que ce noyau pourrait jouer un rôle dans les processus de planification d'un mouvement oculaire. ...
Une très grande majorité de nos activités quotidiennes (lire un livre, conduire une voiture, apprécier une œuvre d’art) sont guidées par la vision active, c’est-à-dire l’interaction dynamique et constante entre notre système visuel, qui nous permet d’acquérir la représentation de la scène qui nous entoure et notre système oculomoteur, qui nous permet de déplacer notre regard de façon brève et rapide (‘saccades oculaires’) d’un objet à un autre au sein de cette scène. L’interaction entre ces deux systèmes est éminemment remarquable puisque malgré ces déplacements balistiques de l’œil, nous arrivons systématiquement à : (1) diriger notre regard de façon précise sur le stimulus d’intérêt en dépit de perturbations physiologiques ou pathologiques et (2) à maintenir une représentation visuelle stable de l’environnement malgré l’exécution de la saccade qui pourrait générer une image floutée ou instable en raison de sa haute vitesse. Ceci est respectivement permis par deux processus : (1) un mécanisme de plasticité sensori-motrice appelé adaptation saccadique qui assure le contrôle permanent de nos mouvements oculaires et (2) un système prédictif qui permet d’anticiper l’image visuelle post-saccadique. L’objectif de cette thèse était de mieux comprendre comment les prédictions de nos actions oculomotrices structurent -du moins en partie- notre perception visuelle par trois études. La première a été menée auprès d’un patient présentant une lésion du cortex pariétal postérieur. Elle a permis de valider deux hypothèses : (1) un signal de prédiction du mouvement oculaire est -sous certaines conditions- nécessaire pour localiser de façon précise une cible visuelle après une saccade et (2) le cortex pariétal postérieur joue un rôle clé dans son intégration. Les études 2 et 3 ont été menées respectivement auprès d’un groupe de volontaires sains et de patients cérébelleux. Elles visaient à comprendre comment une phase de plasticité oculomotrice (induisant une discordance systématique entre l’image prédite et réelle de la scène visuelle post-saccadique -qui devait nécessairement être corrigée par le mécanisme d’adaptation-) altérait notre capacité à localiser précisément un objet dans l’espace. Les résultats obtenus ont montré que la correction oculomotrice de cette discordance était effective chez le sujet sain et entraînait en contrepartie un biais perceptif de localisation. En revanche, la lésion du cervelet entravait la capacité de ces patients à corriger cette discordance, ce qui leur permettait de maintenir des jugements de localisation précis. Enfin, deux patients présentaient une dissociation entre capacité d’adaptation et performances de localisation spatiale. Dans l’ensemble, ces données suggèrent que le cervelet joue un rôle clé à la fois dans les fonctions motrices mais aussi dans la transmission de signaux prédictifs au cortex cérébral pour la perception visuo-spatiale et que ces deux fonctions sont sous-tendues par des territoires cérébelleux distincts. Au-delà de l’aspect fondamental, les tâches expérimentales que nous avons utilisées dans ces études pourraient s’avérer utiles en tant que biomarqueurs afin d’identifier une atteinte précoce de ce codage prédictif, ce qui a été couramment documenté en contexte psychiatrique, notamment dans le cas de schizophrénie.
... Concernant le rôle de ce noyau dans l'oculomotricité de façon large, nous pouvons souligner qu'il reçoit des afférences du NRTP et projette vers plusieurs centres oculomoteurs tels que la PPRF et le noyau interstitiel de Cajal ou même vers les motoneurones du muscle droit latéral par une voie tri-synaptique (Prevosto et al., 2017). Les neurones du noyau dentelé contenus dans sa partie caudale sont caractérisés par une activité similaire à celle des LLBNs liée à la préparation des saccades oculaires (Ashmore & Sommer, 2013;Hepp et al., 1982) et à la prédiction d'événements sensoriels (Ohmae et al., 2013). Parallèlement, certains neurones localisés dans sa partie rostrale présentent une activité de type SLBN qui précède le début du mouvement (W. A. MacKay, 1988), ce qui suggère que ce noyau pourrait jouer un rôle dans les processus de planification d'un mouvement oculaire. ...
Une très grande majorité de nos activités quotidiennes (lire un livre, conduire une voiture, apprécier une œuvre d’art) sont tributaires de notre vision active, c’est-à-dire de l’interaction dynamique et constante entre notre système visuel, qui nous permet d’acquérir la représentation de la scène qui nous entoure et notre système oculomoteur, qui nous permet de déplacer notre regard entre les éléments d’intérêt de cette scène. L’interaction entre ces deux systèmes est éminemment remarquable puisque : (1) diriger notre regard sur des stimuli d’intérêt s’effectue de façon brève et rapide par des mouvements balistiques (‘saccades’) et néanmoins précis de l’œil en dépit de perturbations physiologiques ou pathologiques et (2) une représentation visuelle stable de l’environnement est maintenue malgré les très fortes perturbations des images captées par les rétines que génère l’exécution des saccades. Cette performance est respectivement permise par deux processus : (1) un mécanisme de plasticité sensorimotrice appelé adaptation saccadique qui assure le contrôle permanent de nos mouvements oculaires et (2) un système prédictif qui permet d’anticiper l’image visuelle post-saccadique.
L’objectif de cette thèse était de mieux comprendre comment et dans quelle mesure les prédictions de nos actions oculomotrices structurent notre perception visuelle. Trois études ont été conduites dans ce but. La première a été menée auprès d’un patient présentant une lésion du cortex pariétal postérieur. Elle a permis de démontrer que : (1) un signal de prédiction du mouvement oculaire est nécessaire pour localiser de façon précise une cible visuelle après une saccade et (2) le cortex pariétal postérieur joue un rôle clé dans la prise en compte de ce signal pour maintenir une image post-saccadique cohérente de l’environnement. Les études 2 et 3 ont été menées respectivement auprès d’un groupe de volontaires sains et de patients cérébelleux. Elles visaient à comprendre comment l’induction d’une plasticité oculomotrice peut altérer notre capacité à localiser précisément un objet dans l’espace. Les résultats obtenus chez les sujets sains ont montré que la correction oculomotrice adaptative de la discordance induite entre l’image prédite et réelle de la scène visuelle post-saccadique était effective et s’accompagnait d’un biais perceptif de localisation. En revanche, la lésion du cervelet entravait la capacité des patients à corriger cette discordance, ce qui leur permettait paradoxalement de réaliser des jugements de localisation plus précis que les sujets sains. Enfin, deux patients présentaient une dissociation entre capacité d’adaptation et performance de localisation spatiale. Ces données suggèrent que le cervelet joue un rôle clé à la fois dans les fonctions motrices mais aussi dans la transmission de signaux prédictifs au cortex cérébral pour la perception visuo-spatiale. Au-delà de l’aspect fondamental de ces résultats, nous proposons que les tâches expérimentales que nous avons utilisées dans ces études pourraient s’avérer utiles afin de mieux comprendre certains troubles psychiatriques (e.g., la schizophrénie) où la perturbation de ce codage prédictif a été documenté.
... In addition, the same cells in the lateral cerebellum displayed modulated SS signals in the instruction period in both pro-and antisaccade trials and showed more prominent saccade-related activity at the population level. PCs in the medial cerebellum were more sensitive to trial history, and PCs of the suppression category in this region showed a relatively late SS modulation during execution of both pro-and antisaccades, in line with previous findings 25,40,41 . ...
... However, given that all these regions are both downstream and upstream connected with the cerebellum 15 , the cerebellum may well form an additional hub in this voluntary motor control circuitry [16][17][18][19][20] . This possibility is corroborated by recent findings that the cerebellum does not only participate in movement execution, but also in movement planning [21][22][23][24][25] . Yet, whether and how the cerebellum may contribute to the inhibition of a prepotent response and executive control thereof remains to be elucidated. ...
Consciously suppressing responses to distracting external stimuli helps us to reach our goals. This volitional inhibition of a specific behavior is supposed to be mainly mediated by the cerebral cortex; however recent evidence supports the involvement of the cerebellum in this process. It is currently not known whether different parts of the cerebellar cortex play differential or synergistic roles in planning and execution of this behavior. Here, we measured Purkinje cell (PC) responses in the medial and lateral cerebellum in two rhesus macaques during the antisaccade task. In this task the non-human primates were instructed to make a saccadic eye movement away from a target, rather than towards it. Our data shows that the cerebellum plays an important role not only during execution of the antisaccades, but also during the volitional inhibition of eye movements towards the target. Simple Spike (SS) modulation during the instruction and execution period of pro- and antisaccades is prominent in PCs of both medial and lateral cerebellum. However, only the SS activity in the lateral cerebellar cortex contains information about trial identity and shows a stronger reciprocal interaction with complex spikes. Moreover, SS activity of different PC groups modulate bidirectionally in both regions, but the PCs that show facilitating and suppressive activity are predominantly associated with instruction and execution, respectively. These findings show that different cerebellar regions and PC groups contribute to goal-directed behavior and volitional inhibition, but with different propensities, highlighting the rich repertoire of cerebellar control in executive functions.
Significance Statement
The antisaccade task is commonly used in research and clinical evaluation as a test of conscious and flexible control of behavior. It requires volitional suppression of prosaccades, a function that has been attributed to the neocortex. However, recent findings indicate that cerebellum also contributes to this behavior. We recorded from neurons in the medial and lateral cerebellum to evaluate their responses in this task. We found that both regions significantly modulated their activity during this task, but only cells in the lateral cerebellum encoded the stimulus identity in each trial. These results indicate that the cerebellum actively contributes to the control of flexible behavior and that lateral and medial cerebellum play different roles during volitional eye movements.
... For example, single neuron responses in substantia nigra pars reticulata that were strongly modulated by reward schedule (Yasuda and Hikosaka, 2015) can influence neural responses in the thalamus. Finally, the cerebellum plays a central role in trial-by-trial calibration of motor variables (Ito, 2002;Medina and Lisberger, 2008;Herzfeld et al., 2015) including movement initiation time (Ashmore and Sommer, 2013;Kunimatsu et al., 2018;Narain et al., 2018) and thus is a natural candidate for calibrating firing rates in thalamus, although how such calibration could be made reward-sensitive remains an open question (Hoshi et al., 2005). In sum, our work provides behavioral, modeling, and neurophysiological evidence in support of the hypothesis that the brain uses reinforcement to regulate behavioral variability in a context-dependent manner. ...
Learning reduces variability but variability can facilitate learning. This paradoxical relationship has made it challenging to tease apart sources of variability that degrade performance from those that improve it. We tackled this question in a context-dependent timing task requiring humans and monkeys to flexibly produce different time intervals with different effectors. We identified two opposing factors contributing to timing variability: slow memory fluctuation that degrades performance and reward-dependent exploratory behavior that improves performance. Signatures of these opposing factors were evident across populations of neurons in the dorsomedial frontal cortex (DMFC), DMFC-projecting neurons in the ventrolateral thalamus, and putative target of DMFC in the caudate. However, only in the thalamus were the performance-optimizing regulation of variability aligned to the slow performance-degrading memory fluctuations. These findings reveal how variability caused by exploratory behavior might help to mitigate other undesirable sources of variability and highlight a potential role for thalamocortical projections in this process.
... GABAergic nucleo-olivary neurons, abundant in the other cerebellar nuclei (Prekop et al., 2018), are relatively sparsely distributed in each subregion of the fastigial nucleus (Ruigrok and Teune, 2014). Interestingly, as with fastigial F3 and F4 neurons, small glutamatergic neurons in the dentate (lateral) cerebellar nucleus are located ventrally and are associated with nonmotor functions of the cerebellum (Dum et al., 2002;Küper et al., 2011;Ashmore and Sommer, 2013;Kunimatsu et al., 2016). ...
The cerebellar vermis, long associated with axial motor control, has been implicated in a surprising range of neuropsychiatric disorders and cognitive and affective functions. Remarkably little is known, however, about the specific cell types and neural circuits responsible for these diverse functions. Here, using single-cell gene expression profiling and anatomical circuit analyses of vermis output neurons in the mouse fastigial (medial cerebellar) nucleus, we identify five major classes of glutamatergic projection neurons distinguished by gene expression, morphology, distribution, and input-output connectivity. Each fastigial cell type is connected with a specific set of Purkinje cells and inferior olive neurons and in turn innervates a distinct collection of downstream targets. Transsynaptic tracing indicates extensive disynaptic links with cognitive, affective, and motor forebrain circuits. These results indicate that diverse cerebellar vermis functions could be mediated by modular synaptic connections of distinct fastigial cell types with posturomotor, oromotor, positional-autonomic, orienting, and vigilance circuits.
... GABAergic nucleo-olivary neurons, abundant in the other cerebellar nuclei (Prekop et al., 2018), are relatively sparsely distributed in each subregion of the fastigial nucleus (Ruigrok and Teune, 2014). Interestingly, as with fastigial F3 and F4 neurons, small glutamatergic neurons in the dentate (lateral) cerebellar nucleus are located ventrally and are associated with nonmotor functions of the cerebellum (Dum et al., 2002;Küper et al., 2011;Ashmore and Sommer, 2013;Kunimatsu et al., 2016). ...
The cerebellar vermis, long associated with axial motor control, has been implicated in a surprising range of neuropsychiatric disorders and cognitive and affective functions. Remarkably little is known, however, about the specific cell types and neural circuits responsible for these diverse functions. Here, using single-cell gene expression profiling and anatomical circuit analyses of vermis output neurons in the mouse fastigial (medial cerebellar) nucleus, we identify five major classes of glutamatergic projection neurons distinguished by gene expression, morphology, distribution, and input-output connectivity. Each fastigial cell type is connected with a specific set of Purkinje cells and inferior olive neurons and in turn innervates a distinct collection of downstream targets. Transsynaptic tracing indicates extensive disynaptic links with cognitive, affective, and motor forebrain circuits. These results indicate that diverse cerebellar vermis functions could be mediated by modular synaptic connections of distinct fastigial cell types with posturomotor, oromotor, positional-autonomic, orienting, and vigilance circuits.
