Abstract
BACKGROUND: The medial prefrontal cortex (mPFC) is essential for social behaviors, yet whether and how it encodes social memory remains unclear. METHODS: 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. RESULTS: 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 D(1) 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. CONCLUSIONS: 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.