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

Cell Rep. 2019 Oct 29;29(5):1099-1112.e4. doi: 10.1016/j.celrep.2019.09.044.


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.

Keywords: ErbB4; adolescence; area CA2; delta opioid receptors; hippocampus; long-term depression; neuregulin 1; parvalbumin interneuron; perineuronal net; social memory.

MeSH terms

  • Aging / metabolism
  • Animals
  • Animals, Newborn
  • CA2 Region, Hippocampal / metabolism*
  • Interneurons / metabolism*
  • Long-Term Synaptic Depression
  • Male
  • Memory*
  • Mice
  • Mice, Inbred C57BL
  • Neural Inhibition
  • Neuregulin-1 / metabolism
  • Neuronal Plasticity*
  • Parvalbumins / metabolism*
  • Receptor, ErbB-4 / metabolism*
  • Receptors, Opioid, delta / metabolism
  • Signal Transduction*
  • Social Behavior*
  • Synapses / metabolism
  • gamma-Aminobutyric Acid / metabolism


  • Neuregulin-1
  • Nrg1 protein, mouse
  • Parvalbumins
  • Receptors, Opioid, delta
  • gamma-Aminobutyric Acid
  • Receptor, ErbB-4