Arc-Mediated Plasticity in the Paraventricular Thalamic Nucleus Promotes Habituation to Stress

Corbett, Brian; Luz, Sandra; Arner, Jay; Vigderman, Abigail; Urban, Kimberly R.; Bhatnagar, Seema

doi:10.1016/j.biopsych.2022.02.012

Cited by 10 publications

(23 citation statements)

References 69 publications

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“…There were no effects of sex or restraint on sEPSC frequency, which would suggest changes in the frequency of presynaptic glutamatergic vesicle release. Our ndings of restraint-induced increases in EPSC amplitude and decay time are consistent with our recent nding that expression of the neuronal activity markers c-Fos and Arc is increased in the pPVT of male rats following 1 or 5 days of restraint (17). Thus, increased sEPSC amplitude and EPSC decay time represent two important electrophysiological properties that are consistent with increases in pPVT action potential ring caused by restraint in males.…”

Section: Discussionsupporting

confidence: 92%

“…Together, these ndings suggest that, compared to females, the passive membrane properties of pPVT neurons of male rats make them more likely to re action potentials in response to excitatory inputs. Therefore, in addition to restraint-induced increases in sEPSC amplitude and decay time, a more depolarized resting membrane potential and restraint-induced increases in input resistance may further contribute to the observation that pPVT activity is increased by restraint male rats (17).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, increased sEPSC amplitude and EPSC decay time represent two important electrophysiological properties that are consistent with increases in pPVT action potential ring caused by restraint in males. Because pPVT activity is necessary for habituation (17,50), these electrophysiological properties may contribute to habituation in male rats. In female rats, sEPSC amplitude is unchanged by restraint and sEPSC decay time is reduced by restraint.…”

Section: Discussionmentioning

confidence: 99%

“…Addiction (60, 61) and ADHD (62) are both heavily in uenced by the rewarding and reinforcing effects of dopaminergic neurotransmission. The PVT receives dopaminergic inputs (63) and is an important regulator of reward (64-66) and attention (17). Therefore, reduced Kcnj6 expression could contribute to addiction and/or attention de cits in stressed animals.…”

Section: Discussionmentioning

confidence: 99%

“…Chemogenetic inhibition of the posterior division of the PVT (pPVT) or excitatory lesions impair behavioral and neuroendocrine habituation in male rats (7,17). The PVT is an extensive midline thalamic nucleus (18-23) that receives afferents from the nucleus tractus solitarius, parabrachial nuclei, locus coeruleus, raphe nuclei, prefrontal cortex, amygdala, and the suprachiasmatic nuclei (20,22,(24)(25)(26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

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Sex differences in electrophysiological properties and voltage-gated ion channel expression in the paraventricular thalamic nucleus following repeated stress

Bhatnagar

Corbett

Urban

et al. 2022

Preprint

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Habituation to repeated stress refers to a progressive reduction in the stress response following multiple exposures to the same, predictable stressor. We previously demonstrated that the posterior division of the paraventricular thalamic nucleus (pPVT) nucleus regulates habituation to 5 days of repeated restraint stress in male rats. Compared to males, female rats display impaired habituation to 5 days of restraint. To better understand how activity of pPVT neurons is differentially impacted in stressed males and females, we examined the electrophysiological properties of pPVT neurons under baseline conditions or following restraint. We report here that spontaneous excitatory post-synaptic current (sEPSC) amplitude was increased in males, but not females, following restraint. Further, resting membrane potential of pPVT neurons was more depolarized in males. This may be partially due to reduced potassium leakage in restrained males as input resistance was increased in male, but not female, rats 24 hours following 1 or 5 days of 30-minute restraint. Reduced potassium efflux during action potential firing also occurred in males following a single restraint as action potential half-width was increased following a single restraint. Restraint had limited effects on electrophysiological properties in females, although the mRNA for 10 voltage-gated ion channel subunits was altered in the pPVT of female rats. We hypothesize that restraint-induced changes in pPVT activation promote habituation in males. These findings are the first to describe a sexual dimorphism in stress-induced electrophysiological properties and voltage-gated ion channel expression in the pPVT. These results may explain, at least in part, why habituation to 5 days of restraint is disrupted in female rats.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sex differences in electrophysiological properties and voltage-gated ion channel expression in the paraventricular thalamic nucleus following repeated stress

Bhatnagar

Corbett

Urban

et al. 2022

Preprint

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Sphingosine-1-phosphate receptor 3 activation promotes sociability and regulates transcripts important for anxiolytic-like behavior

Castro-Vildosola,

Bryan,

Tajamal

et al. 2025

Brain, Behavior, and Immunity

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Differential recruitment of brain circuits during fear extinction in non-stressed compared to stress resilient animals

Pearson-Leary,

Abramenko,

Estela-Pro

et al. 2024

Sci Rep

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Dysfunctional fear responses in post-traumatic stress disorder (PTSD) may be partly explained by an inability to effectively extinguish fear responses elicited by trauma-related cues. However, only a subset of individuals exposed to traumatic stress develop PTSD. Therefore, studying fear extinction deficits in animal models of individual differences could help identify neural substrates underlying vulnerability or resilience to the effects of stress. We used a rat model of social defeat in which rats segregate into passively and actively coping rats. In previous work, we showed that passively coping rats exhibit disruptions in social interaction whereas actively coping rats do not display behaviors differently from controls, indicating their resilience. Here, adult male rats exposed to 7 days of social defeat were tested for fear extinction, retention of extinction, and persistence of retention using contextual fear and ethologically-relevant fear tests. Passively coping rats exhibited elevated freezing in response to the previously extinguished context. Analyses of cFos expressing cells across select brain regions showed high correlations within dorsal hippocampal subregions, while passively coping rats had high correlations between the dorsal hippocampus CA1 and the central and basolateral subregions of the amygdala. Importantly, although control and actively coping rats showed similar levels of behavioral extinction, there was little similarity between activated structures, suggesting stress resilience in response to chronic social defeat involves an adaptive differential recruitment of brain circuits to successfully extinguish fear memories.

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Arc-Mediated Plasticity in the Paraventricular Thalamic Nucleus Promotes Habituation to Stress

Cited by 10 publications

References 69 publications

Sex differences in electrophysiological properties and voltage-gated ion channel expression in the paraventricular thalamic nucleus following repeated stress

Sex differences in electrophysiological properties and voltage-gated ion channel expression in the paraventricular thalamic nucleus following repeated stress

Sphingosine-1-phosphate receptor 3 activation promotes sociability and regulates transcripts important for anxiolytic-like behavior

Differential recruitment of brain circuits during fear extinction in non-stressed compared to stress resilient animals

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