Distinct subpopulations of parvalbumin neurons participating in divergent prefrontal functions.

Abstract

Prefrontal parvalbumin (PV) neurons play crucial roles in various distinct functions, while malfunction of PV-neurons also has critical contributions to various brain diseases, including both psychiatric and neurodegenerative disorders. However, whether the prefrontal cortex (PFC) PV-neurons participating in these functions and malfunctions are distinct subpopulations is not well understood. This question is important for a better understanding of both the basic properties/function of PV-neurons and inhibitory neurons in general, and for potential comorbid occurrence of dysfunctions in disease settings. Here, we analyzed dorsomedial prefrontal cortex (dmPFC) PV-neurons participating in working memory, modulation of conditioned fear memory, and anxiety, regarding their relative localization, electrophysiological properties, and synaptic inputs. In addition, by using activity-dependent tagging method, we examined whether manipulating the dmPFC PV-neurons participating in one function may affect another function as a way to test for potential functional interactions between them. We found that: (1) one single group of dmPFC PV-neurons participating in the two forms of modulation of conditioned fear memory, based on their high overlap in localization and mutual functional interactions with each other. (2) dmPFC PV-neurons participating in fear memory modulation and anxiety are two different subpopulations, with unique electrophysiological properties. (3) dmPFC PV-neurons participating in working memory and fear memory modulation are two different subpopulations, with different synaptic and neuronal properties. These findings provide important insights into the organization of PV-neurons in the PFC and highlight the distinct and non-interacting nature of different PV-subpopulations in the PFC functional diversity.