GABA neurons of the ventral periaqueductal gray area modulate behaviors associated with anxiety and conditioned fear.

Abstract

Emotional behavioral responses related to anxiety and fear comprise the negative valence systems domainas defined by the Research Domain Criteria (RDoC) approach to categorizing related emotional behavioral constructs that are compromised in mental health disorders. Here, we evaluate the role of GABA neurons of the ventral periaqueductal gray (vPAG) in emotional behavioral responses related to anxiety and fear using a chemogenetic approach in Vgat-ires-Cre mice. Functional inhibition of vPAG GABA neurons using selective expression of inhibitory Gi-coupled Designer Receptors Exclusively Activated by Designer Drugs (Gi-DREADDs) enhanced anxiety-like behavior in the light-dark exploration and open-field tests. Functional inhibition of vPAG GABA neurons during the acquisition of conditioned fear impaired later performance of conditioned fear responses to the fear-associated context. No effects on spontaneous freezing behavior, fear generalization, or conditioned fear responses to the fear-associated cue were observed. Together, these data suggest that activity of vPAG GABA neurons underlies emotional behavioral responses related to anxiety and conditioned fear. As such, vPAG GABA neurons are a common neurophysiological correlate of the negative valence system and dysregulation of this population may contribute to the etiology of mental health disorders in which the negative valence systems domain is compromised.