Dataset Information

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

ABSTRACT:

Background

Habituation is defined as a progressive decline in response to repeated exposure to a familiar and predictable stimulus and is highly conserved across species. Disrupted habituation is a signature of posttraumatic stress disorder. In rodents, habituation is observed in neural, neuroendocrine, and behavioral responses to repeated exposure to predictable and moderately intense stress or restraint. We previously demonstrated that lesioning the posterior paraventricular thalamic nucleus (pPVT) impairs habituation. However, the underlying molecular mechanisms and specific neural connections among the pPVT and other brain regions that underlie habituation are unknown.

Methods

Behavioral and neuroendocrine habituation was assessed in adult male Sprague Dawley rats using the repeated restraint paradigm. Pan-neuronal and Cre-dependent DREADDs (designer receptors exclusively activated by designer drugs) were used to chemogenetically inhibit the pPVT and the subpopulation of pPVT neurons that project to the medial prefrontal cortex (mPFC), respectively. Activity-regulated cytoskeleton-associated protein (Arc) expression was knocked down in the pPVT using small interfering RNA. Structural plasticity of pPVT neurons was assessed using Golgi staining. Local field potential recordings were used to assess coherent neural activity between the pPVT and mPFC. The attentional set shifting task was used to assess mPFC-dependent behavior.

Results

Here, we show that Arc promotes habituation by increasing stress-induced spinogenesis in the pPVT, increasing coherent neural activity with the mPFC, and improving mPFC-mediated cognitive flexibility.

Conclusions

Our results demonstrate that Arc induction in the pPVT regulates habituation and mPFC function. Therapies that improve synaptic plasticity during posttraumatic stress disorder therapy may enhance habituation and the efficacy of posttraumatic stress disorder treatment.

SUBMITTER: Corbett BF

PROVIDER: S-EPMC9246972 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Corbett Brian F BF Luz Sandra S Arner Jay J Vigderman Abigail A Urban Kimberly K Bhatnagar Seema S

Biological psychiatry 20220221 2

<h4>Background</h4>Habituation is defined as a progressive decline in response to repeated exposure to a familiar and predictable stimulus and is highly conserved across species. Disrupted habituation is a signature of posttraumatic stress disorder. In rodents, habituation is observed in neural, neuroendocrine, and behavioral responses to repeated exposure to predictable and moderately intense stress or restraint. We previously demonstrated that lesioning the posterior paraventricular thalamic n ...[more]

PMID: 35527070

Similar Datasets

Project description:The paraventricular thalamic nucleus (PVT) is a small but highly connected nucleus of the dorsal midline thalamus. The PVT has garnered recent attention as a context-sensitive node within the thalamocortical arousal system that modulates state-dependent motivated behaviors. Once considered related to generalized arousal responses with non-specific impacts on behavior, accumulating evidence bolsters the contemporary view that discrete midline thalamic subnuclei belong to specialized corticolimbic and corticostriatal circuits related to attention, emotions, and cognition. However, the functional connectivity patterns of the human PVT have yet to be mapped. Here, we combined high-quality, high-resolution 7T and 3T resting state MRI data from 121 young adult participants from the Human Connectome Project (HCP) and thalamic subnuclei atlas masks to investigate resting state functional connectivity of the human PVT. The 7T results demonstrated extensive positive functional connectivity with the brainstem, midbrain, ventral and dorsal medial prefrontal cortex (mPFC), anterior and posterior cingulate, ventral striatum, hippocampus, and amygdala. These connections persist upon controlling for functional connectivity of the rest of the thalamus. Whole-brain contrasts provided further evidence that, compared to three nearby midline thalamic subnuclei, functional connectivity of the PVT is strong with the hippocampus, amygdala, ventral and dorsal mPFC, and middle temporal gyrus. These findings suggest that, even during rest, the human PVT is functionally coupled with many regions known to be structurally connected to rodent and non-human primate PVT. Further, cosine similarity analysis results suggested the PVT is integrated into the default mode network (DMN), an intrinsic connectivity network associated with episodic memory and self-referential thought. The current work provides a much-needed foundation for ongoing and future work examining the functional roles of the PVT in humans.

Project description:As one of the thalamic midline nuclei, the thalamic paraventricular nucleus (PVT) is considered to be an important signal integration site for many descending and ascending pathways that modulate a variety of behaviors, including feeding, emotions, and drug-seeking. A recent study has demonstrated that the PVT is implicated in the acute visceral pain response, but it is unclear whether the PVT plays a critical role in the central processing of chronic pain. Here, we report that the neurons in the posterior portion of the PVT (pPVT) and their downstream pathway are involved in descending nociceptive facilitation regarding the development of neuropathic pain conditions in male rats. Lesions or inhibition of pPVT neurons alleviated mechanical allodynia induced by spared nerve injury (SNI). The excitability of pPVT-central amygdala (CeA) projection neurons was significantly increased in SNI rats. Importantly, selective optogenetic activation of the pPVT-CeA pathway induced obvious mechanical hypersensitivity in naive rats. In addition, we used rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques to define a novel neuronal circuit in which glutamatergic neurons in the vlPAG were the target of the pPVT-CeA descending facilitation pathway. Our data suggest that this pPVTGlu+-CeA-vlPAGGlu+ circuit mediates central mechanisms of descending pain facilitation underlying persistent pain conditions.SIGNIFICANCE STATEMENT Studies have shown that the interactions between the posterior portion of the thalamic paraventricular nucleus (pPVT) and central amygdala (CeA) play a critical role in pain-related emotional regulation. However, most reports have associated this circuit with fear and anxiety behaviors. Here, an integrative approach of behavioral tests, electrophysiology, and immunohistochemistry was used to advance the novel concept that the pPVT-CeA pathway activation facilitates neuropathic pain processing. Using rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques, we found that glutamatergic neurons in the vlPAG were the target of the pPVT-CeA pathway. Thus, this study indicates the involvement of a pPVTGlu+-CeA-vlPAGGlu+ pathway in a descending facilitatory mechanism underlying neuropathic pain.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets