The role of the GABAA receptor Alpha 1 subunit in the ventral hippocampus in stress resilience.

Pre-pubertal stress increases post-traumatic stress disorder (PTSD) susceptibility. We have previously demonstrated that enriched environment (EE) intervention immediately after pre-pubertal stress protects from the effects of trauma in adulthood. Here, we examined whether exposure to EE would also be beneficial if applied after exposure to trauma in adulthood. We have recently shown that exposure to juvenile stress and under-water trauma (UWT) is associated with increased expression of GABAA receptor subunit α1 in the ventral hippocampus. However, differentiating between affected and unaffected individuals, this increased expression was confined to stress-exposed, behaviorally unaffected individuals, suggesting upregulation of α1 expression as a potential mechanism of resilience. We now examined whether EE-induced resilience renders increased expression of α1 in the ventral hippocampus redundant when facing a trauma later in life. Adult rats were exposed to UWT, with pre-exposure to juvenile stress, and tested in the open field and elevated plus maze paradigms four weeks later. EE exposure during juvenility prevented pre-pubertal stress-induced vulnerability, but not if performed following UWT in adulthood. Furthermore, juvenile EE exposure prevented the trauma-associated increase in α1 expression levels. Our findings emphasize the importance of early interventions in order to reduce the likelihood of developing psychopathologies in adulthood.

Exposure to prolonged controllable or uncontrollable stress affects GABAergic function in sub-regions of the hippocampus and the amygdala.

The degree of behavioral control that an individual has over a stressor can critically determine its behavioral and neurochemical outcomes. Exposure to uncontrollable stress was previously shown to have detrimental effects on behavior, whereas exposure to equivalent controllable stress prevented these negative outcomes and even improved later stress coping. As many lines of evidence show, stress exposure can have maladaptive changes on inhibitory circuitry, and these effects were largely shown in the hippocampus and amygdala. In the current study we set out to examine alterations in GABAergic activity following exposure to the prolonged two way shuttle (TWS) avoidance task, focusing on the GABA-related factors glutamate decarboxylase (GAD)65, cholecystokinin (CCK) and neuropeptide Y (NPY). As recent views of the hippocampus assume regional specificity in hippocampal function, we examined different regions in the hippocampus, as well as the basolateral amygdala (BLA). Our findings reveal similar alterations in GAD65 in BLA for both controllable and uncontrollable stress exposure, but differential alterations in GAD65 and NPY in the dorsal dentate gyrus (DG). Synaptic plasticity and inhibitory activity in the dorsal DG was further assessed by applying different stimulation protocols and measuring evoked field potentials in vivo. Our results support a role for the DG in stress processing, emphasizing its sensitivity to the nature of the stressor.