Host Interneurons Mediate Cortical Plasticity Reactivated by Embryonic Inhibitory Cell Transplantation

The adult brain lacks sensitivity to changes in the sensory environment found in the juvenile brain. The transplantation of embryonic interneurons has been shown to restore juvenile plasticity to the adult host visual cortex. We show that the transplanted PV interneurons mature, disperse and synaptically integrate into the host brain. However, it is unclear how the integration of transplanted cells re-sensitizes the host brain to visual deprivation. It is not known whether transplanted interneurons directly mediate the renewed cortical plasticity or whether these cells act indirectly by modifying the host interneuron circuitry. Here we find that the transplant-induced reorganization of host circuits is specifically mediated by a developmental signaling pathway Neuregulin (NRG1)/ErbB4 in host parvalbumin (PV) interneurons. It has been shown that during development, NRG1/ErbB4 regulates the excitatory inputs onto PV interneurons. NRG1/ErbB4-mediated loss of excitatory synapses on PV interneurons is necessary for deprivation-induced cortical plasticity in development. Here we show that in transplant recipients, brief visual deprivation reduces the visual activity of host PV interneurons but has negligible effects on the responses of transplanted PV interneurons. Exogenous NRG1 both prevents the deprivation-induced reduction in the visual responses of host PV interneurons and blocks the transplant-induced reorganization of the host circuit. Furthermore, transplantation fails to induce plasticity in recipients that have ErbB4 receptors knocked out specifically in PV interneurons. Altogether, our results indicate that transplanted embryonic interneurons reactivate cortical plasticity by rejuvenating a developmentally restricted signaling pathway in host PV interneurons