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

Abstract

2 HIGHLIGHTS-Infralimbic stimulation increases basal plasma levels of corticosterone.-Environmental enrichment enhances the effects of infralimbic stimulation.-Infralimbic inhibition reduces stress-induced corticosterone in control animals.-Infralimbic cortex contributes to HPA activation during stress and aversive memory. 3 ABSTRACTThe aim of the present study was to investigate the effects of the stimulation and inhibition of the ventral part of the medial prefrontal cortex (infralimbic cortex) on basal and stress-induced plasma levels of corticosterone and on the acquisition of aversive memory in animals maintained in control and environmental enrichment (EE) conditions. Intracortical microinjections of the GABA A antagonist picrotoxin and agonist muscimol were performed in male Wistar rats to stimulate and inhibit, respectively, the activity of the infralimbic cortex. Injections were performed 60 min before foot shock stress and training in the inhibitory avoidance task. Picrotoxin injections into the infralimbic cortex increased basal plasma levels of corticosterone.These increases were higher in EE rats which suggest that EE enhances the control exerted by infralimbic cortex over the hypothalamus-pituitary-adrenal (HPA) axis and corticosterone release. Muscimol injections into the infralimbic cortex reduced the stress-induced plasma levels of corticosterone and the retention latency 24 h after training in the inhibitory avoidance performance in control and EE animals, respectively. These results further suggest that the infralimbic cortex is required for the activation of the HPA axis during stress and for the acquisition of contextual aversive memories.

Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD

“…The procedures for the microinjections and microdialysis experiments were adapted from previous studies of the laboratory (del Arco et al, 2015;Ronzoni et al, 2016). Animals were anesthetized with equithesin (2.5 mg/kg i.p.)…”

High‐Salt Exposure During Perinatal Development Enhances Stress Sensitivity

“…Stimulation of the PL‐PFC, for example, has been demonstrated to inhibit HPA activation to stress (Radley et al, ; Jones et al, ) and inhibition of the PL‐PFC is sufficient to increase heart rate in response to stress‐provoking psychological stimuli (Akana et al, ). Meanwhile, activation of the IL‐PFC has been shown to increase basal plasma levels of CORT (Ronzoni et al, ) as well as blood pressure (Frysztak and Neafsey, ). The observed dendritic spine plasticity in the PL‐PFC and IL‐PFC is therefore intriguing in that it may predispose salt‐exposed offspring to heightened stress sensitivity in a two‐prong fashion, by attenuating and augmenting activity in stress‐repressing and stress‐inducing brain regions, respectively.…”

“…These observations suggest that perinatal salt exposure may serve as an early life stressor, predisposing offspring to diseases of reward dysregulation, much like other forms of stress increase vulnerability to drug use and addiction (Sinha, ). Yet, the effect of early salt exposure on behavior and neuronal morphology in the prefrontal cortex (PFC) and nucleus accumbens (NAc), areas highly involved in both stress (Radley et al, ; Jones et al, ; Ronzoni et al, ) and reward processing (Russo and Nestler, ), remains to be elucidated.…”

Neural oscillations in the infralimbic cortex after electrical stimulation of the amygdala. Relevance to acute stress processing

“…In these experiments it is noteworthy that theta power in the vmPFC specifically increases when the animal reaches the “safe” areas of anxiogenic environments, which has been interpreted as a mechanism for behavioural inhibition. In this context, IL theta rhythm seems to play a crucial role in fear extinction and stress control (Thompson et al, ; Awad, Ferreira, & Maroun, ; Ronzoni, Antón, Mora, Segovia, & Del Arco, ). Indeed corticolimbic theta coupling between the IL and the lateral amygdala has been described for fear extinction conditions, and is considered an example of adaptive inhibitory learning (Lesting et al, ).…”