Maturation of PNN and ErbB4 Signaling in Area CA2 during Adolescence Underlies the Emergence of PV Interneuron Plasticity and Social Memory

Adolescence is a vulnerable period characterized by major cognitive changes. The mechanisms underlying the emergence of new cognitive functions are poorly understood. We find that a long-term depression of inhibitory transmission (iLTD) from parvalbumin-expressing (PV+) interneurons in the hippocampal area Cornu Ammonis 2 (CA2) is absent in young mice but emerges at the end of adolescence. We demonstrate that the maturation of both the perineuronal net (PNN) and signaling through ErbB4 is required for this plasticity. Furthermore, we demonstrate that social recognition memory displays the same age dependence as iLTD and is impaired by targeted degradation of the PNN or iLTD blockade in area CA2. Our data reveal an unusual developmental rule for plasticity at the PV+ interneuron transmission in area CA2 and indicate that this plasticity is involved in the emergence of higher cognitive function, such as social memory formation, in late adolescence. [Display omitted] •Inhibitory plasticity from PV+ interneurons in area CA2 emerges at the end of adolescence•The control of GABA release by the PNN and ErbB4 matures at the end of adolescence•Signaling through the PNN via NRG1 and ErbB4 is required for iLTD induction•Preventing iLTD induction in CA2 in vivo impairs social memory formation Dominguez et al. describe the mechanisms involved in the emergence of a form of long-term plasticity at inhibitory synapses from parvalbumin-expressing interneurons in mouse hippocampal area CA2. Maturation of this plasticity potentially underlies the emergence of social memory during late adolescence.