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Differential rearrangements of apical dendrites in the mPFC after corticosteroids and ADX. Sholl analysis-derived distribution of mPFC layer II/III pyramidal cell apical dendritic material based on distance from cell body. (A, C) Mean length of apical dendrite branches between consecutive 20-lm-spaced concentric spheres of Cgprelimbic (Cg1-3) and IL regions. (B, D) Mean number of intersections of apical dendrite branches with consecutive 20-lm-spaced concentric spheres of Cg-prelimbic and IL regions. See Figure 1 for treatment details. *P \ 0.05 versus VEH. Means and standard error of mean are plotted.
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We previously demonstrated that hypercorticalism induces pronounced volumetric reductions in the rat medial prefrontal cortex (mPFC) and that these structural changes correlate with deficits in executive function. By applying 3-dimensional analysis of Golgi-Cox-stained material, we now demonstrate that corticosteroids can exert differential effects...
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Context 1
... P = 0.942; CONT: 20.25 ± 1.63; CORT: 19.83 ± 1.85; DEX: 19.57 ± 1.33; ADX: 18.88 ± 1.58) (Fig. 1). Sholl analysis of apical dendritic segment lengths and the number of intersections as a function of their distance from the soma revealed an overall effect of treatment (length: F 3,16 = 7.834, P = 0.002; intersections: F 3,16 = 4.888, P = 0.013) (Fig. 2). CORT animals had increased branching in the middle portions of the tree, whereas both DEX-and CORT-treated rats showed a marked reduction of dendritic material at distances greater than 280 lm from the soma when compared with controls (length-CORT: P = 0.003, DEX: P = 0.017; intersections-CORT: P = 0.045, DEX: P = 0.022). ADX led to a ...
Context 2
... reduced by all treatments ( 24.71 ± 3.54, DEX: 25.42 ± 2.74, ADX: 29.00 ± 2.70) (Fig. 1). Sholl analysis of apical dendritic segment lengths and of the number of intersections as a function of their distance from the soma revealed an overall effect of treatment (length: F 3,16 = 9.141, P = 0.001; intersections: F 3,16 = 4.878, P = 0.014) (Fig. 2). DEX-and CORT-treated rats showed marked reductions of dendritic material at distances greater than 160 lm from the soma when compared with controls (length-CORT: P = 0.02, DEX: P = 0.001; intersections-CORT: P = 0.045, DEX: P = 0.020). ADX was accompanied by a reduction of dendritic material between 60 and 120 lm from the soma ...
Citations
... For instance, Lockwood et al., 2022 found responses in these areas to SV on both self-and other-benefitting trials when participants were deciding whether to exert effort. In addition, both areas are sensitive to the effects of stress (Berretz et al., 2021;Cerqueira et al., 2007;King et al., 2009;Kogler et al., 2015;Radley et al., 2005). Thus, we hypothesised that if acute stress results in reduced effort-related prosocial behaviour (e.g. ...
... We focused our analysis on the AI and dACC using anatomical masks independently determined by Lockwood et al., 2022. Both areas were of strong a priori interest as they have been reliably implicated in effort-based decision-making (Chong et al., 2017;Croxson et al., 2009;Engström et al., 2014;Lockwood et al., 2022;Prévost et al., 2010) and show a consistent sensitivity to stress (Ahs et al., 2006;Berretz et al., 2021;Cerqueira et al., 2007;Dedovic et al., 2009;Gathmann et al., 2014;King et al., 2009;Kogler et al., 2015;Morgado et al., 2015;Pruessner et al., 2008;Radley et al., 2005;Starcke and Brand, 2012;Wang et al., 2005). ...
Acute stress can change our cognition and emotions, but what specific consequences this has for human prosocial behaviour is unclear. Previous studies have mainly investigated prosociality with financial transfers in economic games and produced conflicting results. Yet a core feature of many types of prosocial behaviour is that they are effortful. We therefore examined how acute stress changes our willingness to exert effort that benefits others. Healthy male participants – half of whom were put under acute stress – made decisions whether to exert physical effort to gain money for themselves or another person. With this design, we could independently assess the effects of acute stress on prosocial, compared to self-benefitting, effortful behaviour. Compared to controls (n = 45), participants in the stress group (n = 46) chose to exert effort more often for self- than for other-benefitting rewards at a low level of effort. Additionally, the adverse effects of stress on prosocial effort were particularly pronounced in more selfish participants. Neuroimaging combined with computational modelling revealed a putative neural mechanism underlying these effects: more stressed participants showed increased activation to subjective value in the dorsal anterior cingulate cortex and anterior insula when they themselves could benefit from their exerted effort relative to when someone else could. By using an effort-based task that better approximates real-life prosocial behaviour and incorporating trait differences in prosocial tendencies, our study provides important insights into how acute stress affects prosociality and its associated neural mechanisms.
... For instance, Lockwood et al., 2022 found responses in these areas to SV on both self-and other-benefitting trials when participants were deciding whether to exert effort. In addition, both areas are sensitive to the effects of stress (Berretz et al., 2021;Cerqueira et al., 2007;King et al., 2009;Kogler et al., 2015;Radley et al., 2005). Thus, we hypothesised that if acute stress results in reduced effort-related prosocial behaviour (e.g. ...
... We focused our analysis on the AI and dACC using anatomical masks independently determined by Lockwood et al., 2022. Both areas were of strong a priori interest as they have been reliably implicated in effort-based decision-making (Chong et al., 2017;Croxson et al., 2009;Engström et al., 2014;Lockwood et al., 2022;Prévost et al., 2010) and show a consistent sensitivity to stress (Ahs et al., 2006;Berretz et al., 2021;Cerqueira et al., 2007;Dedovic et al., 2009;Gathmann et al., 2014;King et al., 2009;Kogler et al., 2015;Morgado et al., 2015;Pruessner et al., 2008;Radley et al., 2005;Starcke and Brand, 2012;Wang et al., 2005). ...
Acute stress can change our cognition and emotions, but what specific consequences this has for human prosocial behaviour is unclear. Previous studies have mainly investigated prosociality with financial transfers in economic games and produced conflicting results. Yet a core feature of many types of prosocial behaviour is that they are effortful. We therefore examined how acute stress changes our willingness to exert effort that benefits others. Healthy male participants - half of whom were put under acute stress - made decisions whether to exert physical effort to gain money for themselves or another person. With this design, we could independently assess the effects of acute stress on prosocial, compared to self-benefitting, effortful behaviour. Compared to controls (n=45), participants in the stress group (n=46) chose to exert effort more often for self- than for other- benefitting rewards at a low level of effort. Additionally, the adverse effects of stress on prosocial effort were particularly pronounced in more selfish participants. Neuroimaging combined with computational modelling revealed a putative neural mechanism underlying these effects: more stressed participants showed increased activation to subjective value in the dorsal anterior cingulate cortex and anterior insula when they themselves could benefit from their exerted effort relative to when someone else could. By using an effort-based task that better approximates real-life prosocial behaviour and incorporating trait differences in prosocial tendencies, our study provides important insights into how acute stress affects prosociality and its associated neural mechanisms.
... For instance, Lockwood et al. (2022) found responses in these areas to subjective value on both self-and other-benefitting trials when participants were deciding whether to exert effort. In addition, both areas are sensitive to the effects of stress (Berretz et al., 2021;Cerqueira et al., 2007;King et al., 2009;Kogler et al., 2015;Radley et al., 2005). Thus, we hypothesised that if acute stress results in reduced effort-related prosocial behaviour (e.g. ...
... We focused our analysis on the AI and dACC, using anatomical masks independently determined by Lockwood et al. (2022). Both areas were of strong a priori interest as they have been reliably implicated in effort-based decision making (Chong et al., 2017;Croxson et al., 2009;Engström et al., 2015;Lockwood et al., 2022;Prévost et al., 2010) and show a consistent sensitivity to stress (Åhs et al., 2006;Berretz et al., 2021;Cerqueira et al., 2007;Dedovic et al., 2009;Gathmann et al., 2014;King et al., 2009;Kogler et al., 2015;Morgado et al., 2015;Pruessner et al., 2008;Radley et al., 2005;Starcke & Brand, 2012;Wang et al., 2005). ...
Acute stress can change our cognition and emotions, but what specific consequences this has for human prosocial behaviour is unclear. Previous studies have mainly investigated prosociality with financial transfers in economic games and produced conflicting results. Yet a core feature of many types of prosocial behaviour is that they are effortful. We therefore examined how acute stress changes our willingness to exert effort that benefits others. Healthy male participants – half of whom were put under acute stress – made decisions whether to exert physical effort to gain money for themselves or another person. With this design, we could independently assess the effects of acute stress on prosocial, compared to self-benefitting, effortful behaviour. Compared to controls (n=45), participants in the stress group (n=46) chose to exert effort more often for self- than for other- benefitting rewards at a low level of effort. Additionally, the adverse effects of stress on prosocial effort were particularly pronounced in more selfish participants. Neuroimaging combined with computational modelling revealed a putative neural mechanism underlying these effects: more stressed participants showed increased activation to subjective value in the dorsal anterior cingulate cortex and anterior insula when they themselves could benefit from their exerted effort, relative to when someone else could. By using an effort-based task that better approximates real-life prosocial behaviour and incorporating trait differences in prosocial tendencies, our study provides important insights into how acute stress affects prosociality and its associated neural mechanisms.
... For instance, Lockwood et al., 2022 found responses in these areas to SV on both self-and other-benefitting trials when participants were deciding whether to exert effort. In addition, both areas are sensitive to the effects of stress (Berretz et al., 2021;Cerqueira et al., 2007;King et al., 2009;Kogler et al., 2015;Radley et al., 2005). Thus, we hypothesised that if acute stress results in reduced effort-related prosocial behaviour (e.g. ...
... We focused our analysis on the AI and dACC using anatomical masks independently determined by Lockwood et al., 2022. Both areas were of strong a priori interest as they have been reliably implicated in effort-based decision-making (Chong et al., 2017;Croxson et al., 2009;Engström et al., 2014;Lockwood et al., 2022;Prévost et al., 2010) and show a consistent sensitivity to stress (Ahs et al., 2006;Berretz et al., 2021;Cerqueira et al., 2007;Dedovic et al., 2009;Gathmann et al., 2014;King et al., 2009;Kogler et al., 2015;Morgado et al., 2015;Pruessner et al., 2008;Radley et al., 2005;Starcke and Brand, 2012;Wang et al., 2005). ...
Acute stress can change our cognition and emotions, but what specific consequences this has for human prosocial behaviour is unclear. Previous studies have mainly investigated prosociality with financial transfers in economic games and produced conflicting results. Yet a core feature of many types of prosocial behaviour is that they are effortful. We therefore examined how acute stress changes our willingness to exert effort that benefits others. Healthy male participants – half of whom were put under acute stress – made decisions whether to exert physical effort to gain money for themselves or another person. With this design, we could independently assess the effects of acute stress on prosocial, compared to self-benefitting, effortful behaviour. Compared to controls (n=45), participants in the stress group (n=46) chose to exert effort more often for self- than for other- benefitting rewards at a low level of effort. Additionally, the adverse effects of stress on prosocial effort were particularly pronounced in more selfish participants. Neuroimaging combined with computational modelling revealed a putative neural mechanism underlying these effects: more stressed participants showed increased activation to subjective value in the dorsal anterior cingulate cortex and anterior insula when they themselves could benefit from their exerted effort, relative to when someone else could. By using an effort-based task that better approximates real-life prosocial behaviour and incorporating trait differences in prosocial tendencies, our study provides important insights into how acute stress affects prosociality and its associated neural mechanisms.
... NPAS4 regulates CSDS-induced reductions in mPFC dendritic spine density and excitatory synaptic transmission CSDS-induced reduction of dendritic spine density on mPFC pyramidal neurons is a putative pathophysiological underpinning of depression-associated behavior (Cerqueira et al., 2007;Colyn et al., 2019;Liston et al., 2006;McKlveen et al., 2013;Ota and Duman, 2013;Qiao et al., 2016;Qu et al., 2018;Shu and Xu, 2017). As such, we quantified dendritic spine density on deep-layer pyramidal neurons in SC shRNA PFC or Npas4 shRNA PFC mice after CSDS compared to nonstressed mice. ...
Chronic stress can produce reward system deficits (i.e., anhedonia) and other common symptoms associated with depressive disorders, as well as neural circuit hypofunction in the medial prefrontal cortex (mPFC). However, the molecular mechanisms by which chronic stress promotes depressive-like behavior and hypofrontality remain unclear. We show here that the neuronal activity-regulated transcription factor, NPAS4, in the mPFC is regulated by chronic social defeat stress (CSDS), and it is required in this brain region for CSDS-induced changes in sucrose preference and natural reward motivation in the mice. Interestingly, NPAS4 is not required for CSDS-induced social avoidance or anxiety-like behavior. We also find that mPFC NPAS4 is required for CSDS-induced reductions in pyramidal neuron dendritic spine density, excitatory synaptic transmission, and presynaptic function, revealing a relationship between perturbation in excitatory synaptic transmission and the expression of anhedonia-like behavior in the mice. Finally, analysis of the mice mPFC tissues revealed that NPAS4 regulates the expression of numerous genes linked to glutamatergic synapses and ribosomal function, the expression of upregulated genes in CSDS-susceptible animals, and differentially expressed genes in postmortem human brains of patients with common neuropsychiatric disorders, including depression. Together, our findings position NPAS4 as a key mediator of chronic stress-induced hypofrontal states and anhedonia-like behavior.
... For instance, Lockwood et al. (12) found responses in these areas to subjective value on both self-and other-benefitting trials when participants were deciding whether to exert effort. In addition, both areas are sensitive to the effects of stress (24)(25)(26)(27)(28). Thus, we hypothesised that if acute stress results in reduced effort-related prosocial behaviour (e.g. 5, 6), it may do so via a preferential response of these areas to subjective value related to self-compared to other-benefitting decisions in stressed participants. ...
... We focused our analysis on the AI and dACC, using anatomical masks independently determined by Lockwood et al. (12). Both areas were of strong a priori interest as they have been reliably implicated in effort-based decision making (12,21,(39)(40)(41) and show a consistent sensitivity to stress (24)(25)(26)(27)(28)(42)(43)(44)(45)(46)(47)(48). ...
Acute stress can change our cognition and emotions, but what specific consequences this has for prosocial behaviour is unclear. Previous studies have mainly investigated prosociality with financial transfers in economic games and produced conflicting results. We examined how acute stress changes our willingness to exert effort for others, which is a core feature of many types of real-life prosocial behaviour. Participants – half of whom were put under acute stress – made decisions whether to exert physical effort to gain money for themselves or another person. With this design, we could independently assess the effects of acute stress on prosocial, compared to self-benefitting, effortful behaviour. Compared to controls, stressed participants chose to exert effort more often for self- than for other-benefitting rewards. This was particularly pronounced for more selfish participants. Neuroimaging combined with computational modelling revealed a putative neural mechanism underlying these effects: more stressed participants showed increased activation to subjective value in the dorsal anterior cingulate cortex (dACC) and anterior insula when they themselves could benefit from their exerted effort relative to when someone else could. Activation differences in the dACC mediated the effect of perceived stress on effortful prosocial behaviour. Using effort-based paradigms to better approximate real-life prosocial behaviour and incorporating trait differences in prosocial tendencies could be key to understanding how acute stress affects prosociality. Considering the importance of such behaviours for our individual relationships and social cohesion, this highlights the need to tackle the sources of stress and help people better cope with stress when it occurs.
... Two-hour of restraint stress is sufficient to generate anxiety-like behavior in rats 10 days later [30,31], and stressed animals show increased synaptic plasticity in mPFC [32][33][34][35][36][37]. Also, the mPFC has an essential role in different stages of memory [38,39], for example, the consolidation of extinction learning or recalling contexts [40,41], and injuries in the IL-mPFC impair memory extinction [24,40,[42][43][44][45]. ...
Individuals deal with adversity and return to a normal lifestyle when adversity ends. Nevertheless, in specific cases, traumas may be preceded by memory distortions in stress-related malaises, and memory extinction impairment is strictly associated with the symptoms of post-traumatic stress disorder. Glucocorticoids (GCs), the central stress mediator, target mineralocorticoid (MR) and glucocorticoid (GR) receptors and coordinate stress responses. Despite MRs being present in brain regions essential to cognition, emotions, and initial stress processing, such as the medial prefrontal cortex (mPFC), most studies attempt to elucidate the stress-induced deleterious actions of GCs via GR. Therefore, it is necessary to understand the relationship between stress, infralimbic mPFC (IL), and memory and how MR-mediated intracellular signaling influences this relationship and modulates memory extinction. We observed that acutely restraint-stressed male Wistar rats showed high corticosterone (CORT) levels, and previous intra-IL-spironolactone administration (a selective MR antagonist) decreased it 60 min after the stress started. Intra-IL-CORT118335, a novel mixed MR/GR selective modulator, increased CORT throughout stress exposure. Ten days after stress, all rats increased freezing in the memory retrieval test and acquired the aversive contextual memory. During the extinction test, intra-IL injection of spironolactone, but not CORT118335, prevented the stress-impaired memory extinction, suggesting that the IL-MR activity controls CORT concentration, and it is crucial to the establishment of late extinction impairment. Also, the concomitant GR full activation overrode MR blockage. It increased CORT levels leading to the stress-induced extinction memory impairment, reinforcing that the MR/GR balance is crucial to predicting stress-induced behavioral outcomes.
... The region of interest was viewed and traced using a BX51 Olympus microscope (100×objective) attached to Olympus DP50 camera and reconstructed using Neurolucida 8.0 software (MBF Bioscience). All clearly evaluable areas of brain slices, which containing 50-150 μm of secondary dendrites from each imaged soma in layer V/VI, were selected as previously described [45,46]. Nine pyramidal neurons per section and three sections per animal were analyzed. ...
Fear regulation changes as a function of the early life is a key developmental period for the continued maturation of fear neural circuitry. The mechanisms of fear retrieval-induced reconsolidation have been investigated but remain poorly understood. The involvement of prelimbic proBDNF in fear memory extinction and its mediated signaling have been reported previously. Specifically, blocking the proBDNF/p75NTR pathway during the postnatal stage disrupts synaptic development and neuronal activity in adulthood. Given the inherent high expression of proBDNF during the juvenile period, we tested whether the prelimbic proBDNF regulated synaptic and neuronal functions allowing to influencing retrieval-dependent memory processing. By examining the freezing behavior of auditory fear-conditioned rats, we found the high level of the prelimbic proBDNF in juvenile rats enhanced the destabilization of the retrieval-dependent weak but not strong fear memory through activating p75NTR-GluN2B signaling. This modification of fear memory traces was attributed to the increment in the proportion of thin-type spine and promotion in synaptic function, as evidenced by the facilitation of NMDA-mediated EPSCs and GluN2B-dependent synaptic depression at the prelimbic projection. Furthermore, the strong prelimbic theta- and gamma-oscillation coupling predicted the suppressive effect of juvenile proBDNF on the recall of postretrieval memory. Our results critically emphasize the importance of developmental proBDNF for modification of retrieval-dependent memory and provide a potential critical targeting to inhibit threaten memories associated with neurodevelopment disorders.
... The central infusion of MR antagonists impairs the regulation of sensory integration after the evaluation of environmental information and disrupts behavioral adjustment in the Morris water maze, open field and inhibitory avoidance task [68][69][70]. MR is abundantly expressed in the mPFC, and the mPFC shows enhanced synaptic plasticity in rodents submitted to stress [71][72][73]. The mPFC plays a crucial role in the various phases of memory [74,75], in consolidation and recall of aversive memories and extinction learning [76,77], likely contributing to adaptation processes that can drive anxiety in subsequent challenges of similar nature [78]. ...
One-trial tolerance (OTT) is characterized by the lack of anxiolytic-like effects of benzodiazepines in animals submitted to a trial 2 in the elevated plus-maze (EPM) and is described to be influenced by learning mechanisms. Mineralocorticoid receptors (MR) in the infralimbic subregion (IL) of the medial prefrontal cortex (mPFC) are important modulators of emotional learning, but the MR involvement in the establishment of OTT remains unclear. We investigated the effects of intra-IL infusions of RU 28318 (an MR antagonist) on the OTT to the anxiolytic effects of midazolam (MDZ, GABAA-benzodiazepine agonist) in mice exposed to a two-trial protocol in the EPM. First, mice were treated with saline or MDZ (2 mg kg⁻¹, i.p.) 30 minutes before trial 1 or 2 in the EPM, to characterize the OTT. To investigate the role of MR in the OTT, independent groups of mice received intra-IL infusions of vehicle or RU 28318 (5 or 10 ng 0.1 µL⁻¹) immediately before or after first trial in the EPM. Twenty-four hours later, the same mice received injections of saline or MDZ and were re-tested in the EPM. The MDZ decreased anxiety-like behaviors in trial 1, but the same anxiolytic-like effect was not observed in MDZ-mice prior to the second EPM test, confirming the OTT. Blockade of MR in the IL before, but not after, trial 1 restored the anxiolytic effects if MDZ administered in trial 2. These findings indicate that the MR in the IL-mPFC contributing to the OTT by mediating the acquisition, but not the consolidation of emotional learning.
... The reduced level of NR2B may represent the reduced level of NR2B containing NMDA receptors and further leads to impaired function of glutamate projection. Stress also induces the release of corticosterone (Whitnall, 1993), leading to the atrophy of glutamate projections (Cerqueira et al., 2006). The decrease of glutamate projection may lead to adaptation changes of NMDA receptors in the DLS. ...
The distinct preferences between goal‐directed and habit‐directed behaviors involve numerous neurodegenerative and psychiatric disorders. Chronic stress during adulthood biases behavior toward habit‐oriented strategies. However, it remains to be studied how adolescence, as a stage in which brain regions are still undergoing development, suffering stress will affect this preference. Here, we exposed rats to chronic unpredictable stress (CUS) at PND 21 to PND 33 and PND 34 to PND 47 to examine its effect on sugar pellet‐based instrumental behavior in adulthood. We showed that rats exposed to CUS in middle adolescence had a biased goal‐directed strategy rather than a habit‐oriented strategy in adulthood, whereas CUS exposure in early adolescence did not have this effect. Moreover, middle adolescent CUS caused the downregulation of the N‐methyl‐d‐aspartate receptor subtype 2 B (NR2B) in the dorsolateral striatum (DLS) rather than in the dorsomedial striatum (DMS), whereas no change was observed in NR2A or the dopamine D1 receptor (D1R) or the dopamine D2 receptor (D2R) in the DLS. Together, these findings suggest that CUS in middle adolescence inhibits habitual behavior in adulthood and downregulates the expression of NR2B in DLS, providing new evidence to understand the molecular mechanisms of abnormal habitual behaviors induced by adolescent stress.
