Regional Differentiation of the Medial Prefrontal Cortex in Regulating Adaptive Responses to Acute Emotional Stress

Abstract

The medial prefrontal cortex (mPFC) is an important neural substrate for integrating cognitive-affective information and regulating the hypothalamo-pituitary-adrenal (HPA) axis response to emotional stress. mPFC modulation of stress responses is effected in part via the paraventricular hypothalamic nucleus (PVH), which houses both autonomic (sympathoadrenal) and neuroendocrine (HPA) effector mechanisms. Although the weight of evidence suggests that mPFC influences on stress-related PVH outputs are inhibitory, discordant findings have been reported, and such work has tended to treat this cortical region as a unitary structure. Here we compared the effects of lesions of the dorsal versus ventral aspects of mPFC, centered in the prelimbic and infralimbic fields, respectively, on acute restraint stress-induced activation of PVH cell groups mediating autonomic and neuroendocrine responses. Lesions to the dorsal mPFC enhanced restraint-induced Fos and corticotropin-releasing factor (CRF) mRNA expression in the neurosecretory region of PVH. Ablation of the ventral mPFC decreased stress-induced Fos protein and CRF mRNA expression in this compartment but increased Fos induction in PVH regions involved in central autonomic control. Repetition of the experiments in rats bearing retrograde tracer deposits to label PVHautonomic projections confirmed that ventral mPFC lesions selectively increased stress-induced Fos expression in identified preautonomic neurons. Finally, hormonal indices of HPA activation in response to acute stress were augmented after dorsal mPFC lesions and attenuated after ventral mPFC lesions. These results suggest that dorsal and ventral aspects of the mPFC differentially regulate neuroendocrine and autonomic PVH outputs in response to emotional stress.

Infralimbic cortex controls the activity of the hypothalamus–pituitary–adrenal axis and the formation of aversive memory: Effects of environmental enrichment

“…This is in agreement with previous studies which show that infralimbic lesions attenuate stress-induced plasma corticosterone [3] and suggest that the infralimbic cortex facilitates the HPA axis activation and release of corticosterone produced by acute stressful stimuli. Interestingly, previous studies from our laboratory using a similar experimental protocol have shown that the stimulation of prelimbic cortex reduces stress-induced plasma levels of corticosterone [8].…”

“…These results are in agreement with the postulated idea that prelimbic and infralimbic cortices play opposite roles in the regulation of the HPA axis in response to stress [2,3]. In fact, an indirect pathway from the PFC to the paraventricular nucleus of the hypothalamus has been proposed to regulate the HPA axis and the release of corticosterone [3,34]. It is also shown in this study that injections of picrotoxin into the infralimbic cortex seem to increase and decrease the stress-induced corticosterone concentrations in EE and control animals, respectively.…”

“…Interestingly, previous studies from our laboratory using a similar experimental protocol have shown that the stimulation of prelimbic cortex reduces stress-induced plasma levels of corticosterone [8]. These results are in agreement with the postulated idea that prelimbic and infralimbic cortices play opposite roles in the regulation of the HPA axis in response to stress [2,3]. In fact, an indirect pathway from the PFC to the paraventricular nucleus of the hypothalamus has been proposed to regulate the HPA axis and the release of corticosterone [3,34].…”

“…Yet how the PFC exerts this regulation is a matter of debate. Previous studies in rodents suggest that the dorsal (prelimbic) and ventral (infralimbic) parts of the medial PFC exert opposite control on the HPA axis activity and plasma levels of corticosterone in response to stress [2][3][4]. However, most pharmacological and lesion studies are limited to the dorsal part of the medial PFC or do not distinguish between the dorsal and ventral parts [5][6][7][8] and, therefore, the role played by the infralimbic cortex in the regulation of the HPA axis and corticosterone concentrations is still uncertain.…”

Chronic Nicotine Self-Administration Augments Hypothalamic–Pituitary–Adrenal Responses to Mild Acute Stress

“…Medial prefrontal cortex (mPFC) is a brain region that might be modified by chronic nicotine SA. mPFC is an inhibitory regulator of the ACTH/CORT response to a psychological stressor (Radley et al, 2006). Indeed, foot shock induced c-fos expression in mPFC (ie cingulate cortex) (Passerin et al, 2000;Wan et al, 1994), whereas LPS affected the PVN and NTS, and not mPFC (Stone et al, 2006;Takemura et al, 1997).…”