Depression of excitatory synapses onto parvalbumin interneurons in the medial prefrontal cortex in susceptibility to stress

Perova, Z., Delevich, K., Li, B. (2015) Depression of excitatory synapses onto parvalbumin interneurons in the medial prefrontal cortex in susceptibility to stress. Journal of Neuroscience, 35 (7). pp. 3201-3206. ISSN 02706474

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URL: http://www.ncbi.nlm.nih.gov/pubmed/25698754
DOI: 10.1523/JNEUROSCI.2670-14.2015

Abstract

In response to extreme stress, individuals either show resilience or succumb to despair. The prefrontal cortex (PFC) is required for coping with stress, and PFC dysfunction has been implicated in stress-related mental disorders, including depression. Nevertheless, the mechanisms by which the PFC participates in stress responses remain unclear. Here, we investigate the role of parvalbumin (PV) interneurons in the medial PFC (mPFC) in shaping behavioral responses to stress induced by the learned helplessness procedure, in which animals are subjected to an unpredictable and inescapable stressor. PV interneurons in the mPFC were probed and manipulated in knock-in mice expressing the Cre recombinase under the endogenous parvalbumin promoter. Notably, we found that excitatory synaptic transmission onto these neurons was decreased in mice showing helplessness, a behavioral state that is thought to resemble features of human depression. Furthermore, selective suppression of PV interneurons in the mPFC using hM4Di, a DREADD (designer receptor exclusively activated by designer drug), promoted helplessness, indicating that activation of these neurons during stress promotes the establishment of resilient behavior. Our results reveal a cellular mechanism of mPFC dysfunction that may contribute to the emergence of maladaptive behavioral responses in the face of adverse life events.

Item Type: Paper
Uncontrolled Keywords: Depression Learned helplessness Medial prefrontal cortex Parvalbumin interneuron Stress Synapse
Subjects: diseases & disorders > mental disorders > mood disorders > depression
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons

organs, tissues, organelles, cell types and functions > tissues types and functions > prefrontal cortex
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse
CSHL Authors:
Communities: CSHL labs > Li lab
Watson School > Publications
Stanley Institute for Cognitive Genomics
Depositing User: Matt Covey
Date Deposited: 27 Feb 2015 17:47
Last Modified: 06 Nov 2015 20:49
PMCID: PMC4331634
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31242

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