Cognitive, Behavioral and Systems NeuroscienceResearch PaperMedial prefrontal cortex activity can disrupt the expression of stress response habituation
Section snippets
Subjects
Male Sprague–Dawley rats were obtained from Harlan Sprague Dawley Inc. (Indianapolis, IN, USA), and were given at least one-week of acclimation after arrival to the animal facilities at the University of Colorado before surgery (weight range 250–310 g at time of surgery). Rats were housed in pairs in polycarbonate cages with wood shavings until surgery, after which rats were housed individually in same-sized cages. The colony room lights were maintained on a 12-h light/dark cycle, with lights
In situ hybridization and verification of cannula placement
We used in situ hybridization to examine c-fos mRNA expression in brain. Coronal brain sections (14 μm) were cut on a cryostat (Leica Microsystems model 1850), thaw-mounted onto poly-l-lysine-coated slides and stored at −80 °C. Series of sections were collected at the approximate rostral–caudal levels that contain the following brain regions (Paxinos and Watson, 1998): (1) prefrontal cortex (3.2 mm anterior to bregma), (2) lateral septum and piriform cortex (1.2 mm anterior to bregma), (3)
Experiment 1: acute effects of mPFC muscimol microinfusion on corticosterone secretion and c-fos mRNA
We first examined the acute effect of inactivation of neuronal activity in the mPFC (microinfusion of GABA-A receptor agonist) on basal and stressed-induced HPA-axis activity and c-fos mRNA levels. Muscimol or vehicle was microinfused into the mPFC 1 h prior to 30 min restraint or brief handling (no stress control).
Restraint challenge led to a significant increase in HPA-axis activity as assessed by corticosterone (F1,49=82.1, P<0.001) hormone secretion. There was no effect of mPFC muscimol
Discussion
This study supports a role for the mPFC in rats to modulate the expression of stress response habituation to repeated psychological stress. We first examined whether transient neural suppression or neural stimulation in the mPFC had an effect on the HPA-axis response to an initial restraint stress session. Suppression of mPFC neural activity (mPFC muscimol microinfusion) had no effect on stress-induced HPA-axis activity or stress-induced c-fos mRNA throughout a range of restraint-responsive
Acknowledgments
This work was supported by an Institutional Seed Grant from the University of Colorado at Boulder, and by NIH grant MH75968. Our thanks to Chad Osterlund, Anna Janas, Evan Paul, and Michael VanElzakker for technical assistance, and to Drs. Serge Campeau, Heidi Day, Chris Lowry, and Akira Miyake for guidance and discussion.
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2022, Neurobiology of StressCitation Excerpt :Overall, our data support the notion that PL PFC neuronal dynamics undergo a form of habituation to repeated homotypic stress via a progressive blunting of within session increases in overall activity and correlated activity to the point of becoming indistinguishable from each other (based on the failure of PL activity to decode early vs late shock on days 2 and 3). These data are supported by previous studies demonstrating that habituation to repeated stressors requires the dorsal PFC function (Adamec et al., 2012; Katz et al., 2009; Weinberg et al., 2010; Diorio et al., 1993). Despite the novel findings presented herein, there are several limitations to the current study.
Cellular and serotonergic correlates of habituated neuroendocrine responses in male and female rats.
2022, PsychoneuroendocrinologyCitation Excerpt :Like most limbic regulators of the HPA axis, the prefrontal cortex does not project to the PVH directly, but rather through multiple hypothalamic relays. Thus, the potential influence of the frontal cortex may be diminished during repeated restraint or subjugated by several other sources of input to the PVH subserving stress habituation (Radley et al., 2009; Weinberg et al., 2010). Sex-dependent changes in both the size and pattern of immediate early gene and HPA axis responses under acute challenges are often interpreted as informing potential sources and/or root causes for sex differences in stress vulnerability.
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