A Subpopulation of Prefrontal Cortical Neurons Is Required for Social Memory

• Published in: Biological psychiatry (1969) 2021-03, Vol.89 (5), p.521-531
• Main Authors: Xing, Bo, Mack, Nancy R., Guo, Kai-Ming, Zhang, Yu-Xiang, Ramirez, Billy, Yang, Sha-Sha, Lin, Li, Wang, Dong V., Li, Yan-Chun, Gao, Wen-Jun
• Format: Article
• Language: English
• Subjects: Animals; Learning and memory; Memory; Mice; Neurons; Nucleus Accumbens; Prefrontal Cortex; Social Behavior; Social behaviors
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2020.08.023

The medial prefrontal cortex (mPFC) is essential for social behaviors, yet whether and how it encodes social memory remains unclear. We combined whole-cell patch recording, morphological analysis, optogenetic/chemogenetic manipulation, and the TRAP (targeted recombination in active populations) transgenic mouse tool to study the social-associated neural populations in the mPFC. Fos-TRAPed prefrontal social-associated neurons are excitatory pyramidal neurons with relatively small soma sizes and thin-tufted apical dendrite. These cells exhibit intrinsic firing features of dopamine D1 receptor–like neurons, show persisting firing pattern after social investigation, and project dense axons to nucleus accumbens. In behaving TRAP mice, selective inhibition of prefrontal social-associated neurons does not affect social investigation but does impair subsequent social recognition, whereas optogenetic reactivation of their projections to the nucleus accumbens enables recall of a previously encountered but “forgotten” mouse. Moreover, chemogenetic activation of mPFC-to-nucleus accumbens projections ameliorates MK-801–induced social memory impairments. Our results characterize the electrophysiological and morphological features of social-associated neurons in the mPFC and indicate that these Fos-labeled, social-activated prefrontal neurons are necessary and sufficient for social memory.