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Chronic stress has an important impact on the adult brain. However, most of the knowledge on its effects is focused on principal neurons and less on inhibitory neurons. Consequently, recent reports have begun to describe stress-induced alterations in the structure, connectivity and neurochemistry of interneurons. Some of these changes appear to be mediated by certain molecules particularly associated to interneurons, such as the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) and components of the perineuronal nets (PNN), specialized regions of the extracellular matrix. These plasticity-related molecules modulate interneuronal structure and connectivity, particularly of parvalbumin expressing basket interneurons, both during development and adult life. These inhibitory neurons are specially affected after chronic stress and in some stress-related disorders, in which the expression of PSA-NCAM and certain components of PNN are also altered. For these reasons we have decided to study PSA-NCAM, PNN and parvalbumin expressing interneurons after 10 days of chronic restraint stress, a time point in which its behavioral consequences are starting to appear. We have focused initially on the medial prefrontal cortex (mPFC), basolateral amygdala (BLA) and hippocampus, regions affected by stress and stress-related psychiatric diseases, but we have also explored the habenula and the thalamic reticular nucleus (TRN) due to the important presence of PNN and their relationship with certain disorders. PSA-NCAM expression was increased by stress in the stratum lacunosum-moleculare of CA1. Increases in parvalbumin immunoreactive cells were detected in the mPFC and the BLA, but were not accompanied by increases in the number of parvalbumin expressing perisomatic puncta on the somata of principal neurons. The number of PNN was also increased in the mPFC and the habenula, although habenular PNN were not associated to parvalbumin cells. Increased expression of parvalbumin and components of PNN were also detected in the TRN after chronic restraint stress, revealing for the first time substantial effects on this region. Our study shows that, even a short chronic stress protocol, can induce consistent changes in interneuronal plasticity-related molecules in cortical and extracortical regions, which may represent initial responses of inhibitory circuits to counteract the effects of this aversive experience. [ABSTRACT FROM AUTHOR]

The effects of intense stressors can last a long time and may lead to the development of psychiatric disorders, including posttraumatic stress disorder. The basolateral amygdala (BLA) plays a critical role in these diseases and is extremely sensitive to stress. Here, we explored in male and female mice the long-term (35 days) impact of a 24-h restraint stress on BLA circuitry. We used Thy1 -YFP mice to discriminate 2 subpopulations of excitatory neurons, which participate in "Fear-On" (Thy1-) and "Fear-Off" (Thy1+) circuits. The stress decreased the density of parvalbumin (PV) + inhibitory neurons in both sexes but did not alter their dendritic complexity. We also analyzed the perisomatic input of basket interneurons on Thy1 + and Thy1 - neurons, finding sex dependent effects. In males, we did not find alterations in the density of PV+ puncta or in that of cannabinoid receptor 1 (CB1R) + puncta from cholecystokinin+ basket cells. By contrast, in females we found increased the density of PV+ puncta on Thy1+ neurons and reduced on the Thy1- neurons. This adverse experience also reduced in the long term the density of CB1R+ puncta both on Thy1 + and Thy1- cells in females. The expression of the activity marker FosB was not altered in PV+ interneurons and in Thy1 + neurons of stressed animals. The density of perineuronal nets, a specialized region of the extracellular matrix, which covers particularly PV+ interneurons and regulates their connectivity, was increased by stress in male mice. Our findings indicate that a single stressful event can produce long-term alterations in the inhibitory circuits of the BLA, especially on PV+ neurons and their plasticity, and that there is a differential impact depending on the sex and the fear-related circuits involved. • A single intense stressful event alters in the long term the inhibitory circuits of the basolateral amygdala. • Alterations are prominent on PV+ neurons and molecules related to their plasticity. • Differential impact on the inhibitory input of excitatory neurons depending on the fear-related circuit they are involved in. • Some of the long term effects of stress observed in amygdaloid inhibitory circuits are sex specific. [ABSTRACT FROM AUTHOR]