Impact of stress on inhibitory neuronal circuits, our tribute to Bruce McEwen

Abstract

This manuscript is dedicated to the memory of Bruce S. McEwen, to commemorate the impact he had on how we understand stress and neuronal plasticity, and the profound influence he exerted on our scientific careers. The focus of this review is the impact of stressors on inhibitory circuits, particularly those of the limbic system, but we also consider other regions affected by these adverse experiences. We revise the effects of acute and chronic stress during different stages of development and lifespan, taking into account the influence of the sex of the animals. We review first the influence of stress on the physiology of inhibitory neurons and on the expression of molecules related directly to GABAergic neurotransmission, and then focus on specific interneuron subpopulations, particularly on parvalbumin and somatostatin expressing cells. Then we analyze the effects of stress on molecules and structures related to the plasticity of inhibitory neurons: the polysialylated form of the neural cell adhesion molecule and perineuronal nets. Finally, we review the potential of antidepressants or environmental manipulations to revert the effects of stress on inhibitory circuits.

Fig. 1

Overview of the main interneuron subpopulations considered in this review (CCK+, SST+, basket PV+ and chandelier PV + cells), along with their subcellular targets. The expressed molecules that are discussed in this manuscript are also shown (GAD65/67 and VGAT are expressed by every GABAergic neuron, while CB1R is expressed presynaptically in CCK + interneurons of the neocortex).