Dataset Information

New neurons restore structural and behavioral abnormalities in a rat model of PTSD.

ABSTRACT: Post-traumatic stress disorder (PTSD) has been associated with anxiety, memory impairments, enhanced fear, and hippocampal volume loss, although the relationship between these changes remain unknown. Single-prolonged stress (SPS) is a model for PTSD combining three forms of stress (restraint, swim, and anesthesia) in a single session that results in prolonged behavioral effects. Using pharmacogenetic ablation of adult neurogenesis in rats, we investigated the role of new neurons in the hippocampus in the long-lasting structural and behavioral effects of SPS. Two weeks after SPS, stressed rats displayed increased anxiety-like behavior and decreased preference for objects in novel locations regardless of the presence or absence of new neurons. Chronic stress produced by daily restraint for 2 or 6 hr produced similar behavioral effects that were also independent of ongoing neurogenesis. At a longer recovery time point, 1 month after SPS, rats with intact neurogenesis had normalized, showing control levels of anxiety-like behavior. However, GFAP-TK rats, which lacked new neurons, continued to show elevated anxiety-like behavior and enhanced serum corticosterone response to anxiogenic experience. Volume loss in ventral CA1 region of the hippocampus paralleled increases in anxiety-like behavior, occurring in all rats exposed to SPS at the early time point and only rats lacking adult neurogenesis at the later time point. In chronic stress experiments, volume loss occurred broadly throughout the dentate gyrus and CA1 after 6-hr daily stress but was not apparent in any hippocampal subregion after 2-hr daily stress. No effect of SPS was seen on cell proliferation in the dentate gyrus, but the survival of young neurons born a week after stress was decreased. Together, these data suggest that new neurons are important for recovery of normal behavior and hippocampal structure following a strong acute stress and point to the ventral CA1 region as a potential key mediator of stress-induced anxiety-like behavior.

SUBMITTER: Schoenfeld TJ

PROVIDER: S-EPMC6692221 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

New neurons restore structural and behavioral abnormalities in a rat model of PTSD.

Schoenfeld Timothy J TJ Rhee Diane D Martin Laura L Smith Jesse A JA Sonti Anup N AN Padmanaban Varun V Cameron Heather A HA

Hippocampus 20190313 9

Post-traumatic stress disorder (PTSD) has been associated with anxiety, memory impairments, enhanced fear, and hippocampal volume loss, although the relationship between these changes remain unknown. Single-prolonged stress (SPS) is a model for PTSD combining three forms of stress (restraint, swim, and anesthesia) in a single session that results in prolonged behavioral effects. Using pharmacogenetic ablation of adult neurogenesis in rats, we investigated the role of new neurons in the hippocamp ...[more]

PMID: 30865372

Similar Datasets

Project description:Status epilepticus (SE) is a life-threatening emergency that can result in de novo development or worsening of epilepsy. We tested the hypothesis that the aberrant cortical output during neocortical focal status epilepticus (FSE) would induce structural and functional changes in the thalamus that might contribute to hyperexcitability in the thalamocortical circuit. We induced neocortical FSE by unilateral epidural application of convulsant drugs to the somatosensory cortex of anesthetized mice of both sexes. The resulting focal EEG ictal episodes were associated with behavioral seizures consisting of contralateral focal myoclonic activity and persisted for 2-3 h. Ten and 30 days later, brains were processed for either immunohistochemistry (IHC) or in vitro slice recordings. Sections from the center of the thalamic reticular nucleus (nRT, see methods), the ventral posterolateral nucleus (VPL), and the ventral posteromedial nucleus (VPM) from the ventrobasal nucleus (VB) were used to measure density of NeuN-immunoreactive neurons, GFAP-reactive astrocytes, and colocalized areas for VGLUT1 + PSD95- and VGLUT2 + PSD95-IR, presumptive excitatory synapses of cortical and thalamic origins. Whole-cell voltage-clamp recordings were used to measure spontaneous EPSC frequency in these nuclei. We found that the nRT showed no decrease in numbers of neurons or evidence of reactive astrogliosis. In contrast, there were increases in GFAP-IR and decreased neuronal counts of NeuN positive cells in VB. Dual IHC for VGLUT1-PSD95 and VGLUT2-PSD95 in VB showed increased numbers of excitatory synapses, likely of both thalamic and cortical origins. The frequency, but not the amplitude of sEPSCs was increased in nRT and VB neurons. SIGNIFICANCE STATEMENT: Previous reports have shown that prolonged neocortical seizures can induce injury to downstream targets that might contribute to long-term consequences of FSE. Effects of FSE in thalamic structures may disrupt normal thalamo-cortical network functions and contribute to behavioral abnormalities and post-SE epileptogenesis. Our results show that a single episode of focal neocortical SE in vivo has chronic consequences including cell loss in VB nuclei and increased excitatory connectivity in intra-thalamic and cortico-thalamic networks. Additional experiments will assess the functional consequences of these alterations and approaches to mitigate cell loss and alterations in synaptic connectivity.

Project description:Opioid addiction is a chronic, relapsing disorder. Whether addicted individuals are forced to abstain or they decide themselves to quit using drugs, relapse rates are high-especially upon encountering contexts and stimuli associated with prior opioid use. Rodents similarly show context- and cue-induced reinstatement of drug seeking following abstinence, and intriguingly, the neural circuits underlying these relapse-like behaviors differ when abstinence is involuntarily imposed, responding is extinguished, or animals decide themselves to cease taking drug. Here, we employ two complementary rat behavioral models of relapse-like behavior for the highly reinforcing opioid drug remifentanil, and asked whether GABAergic neurons in the ventral pallidum (VPGABA) control opioid seeking under these behavioral conditions. Specifically, we asked how chemogenetically stimulating VPGABA neurons with clozapine-N-oxide (CNO) influences the ability of contextual or discrete remifentanil-paired cues to reinstate drug seeking following either voluntary abstinence (punishment-induced; GroupPunish), or extinction training (GroupExt). In GroupPunish rats, we also chemogenetically inhibited VPGABA neurons, and examined spontaneous VP activity (Fos) during cued reinstatement. In both GroupPunish and GroupExt rats, stimulating Gq-signaling in VPGABA neurons augmented remifentanil reinstatement in a cue- and context-dependent manner. Conversely, engaging inhibitory Gi-signaling in VPGABA neurons in GroupPunish suppressed cue-induced reinstatement, and cue-triggered seeking was correlated with Fos expression in rostral, but not caudal VP. Neither stimulating nor inhibiting VPGABA neurons influenced unpunished remifentanil self-administration. We conclude that VPGABA neurons bidirectionally control opioid seeking regardless of the specific relapse model employed, highlighting their fundamental role in opioid relapse-like behavior across behavioral models, and potentially across species.

Dataset Information

New neurons restore structural and behavioral abnormalities in a rat model of PTSD.

Publications

New neurons restore structural and behavioral abnormalities in a rat model of PTSD.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets