Hippocampal GABAergic interneurons and their co-localized neuropeptides in stress vulnerability and resilience

Abstract

Studies in humans and rodents suggest a critical role for the hippocampal formation in cognition and emotion, but also in the adaptation to stressful events. Successful stress adaptation promotes resilience, while its failure may lead to stress-induced psychopathologies such as depression and anxiety disorders. Hippocampal architecture and physiology is shaped by its strong control of activity via diverse classes of inhibitory interneurons that express typical calcium binding proteins and neuropeptides. Celltype-specific opto- and chemogenetic intervention strategies that take advantage of these biochemical markers have bolstered our understanding of the distinct role of different interneurons in anxiety, fear and stress adaptation. Moreover, some of the signature proteins of GABAergic interneurons have a potent impact on emotion and cognition on their own, making them attractive targets for interventions. In particular, neuropeptide Y is a promising endogenous agent for mediating resilience against severe stress. In this review, we evaluate the role of the major types of interneurons across hippocampal subregions in the adaptation to chronic and acute stress and to emotional memory formation.

Keywords: Dorsal and ventral hippocampus; Fear memory; Interneuron; Neuropeptides; Stress.