Host interneurons mediate plasticity reactivated by embryonic inhibitory cell transplantation in mouse visual cortex

Taylor Nakayama,Xiaoxiao Lin,Dario X Figueroa Velez,Xiaoting Zheng,Kirstie J Salinas,Sunil P Gandhi,Xiangmin Xu,Dhruba Banerjee

doi:10.1038/s41467-021-21097-4

Taylor Nakayama, Xiaoxiao Lin + Show 6 more

Open Access

https://doi.org/10.1038/s41467-021-21097-4

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Journal: Nature Communications	Publication Date: Feb 8, 2021
Citations: 5	License type: open-access

Affiliation: University of California, Irvine

Abstract

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. It is unclear 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 mouse host circuits is specifically mediated by Neuregulin (NRG1)/ErbB4 signaling in host parvalbumin (PV) interneurons. 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. While deletion of ErbB4 receptors from host PV interneurons blocks cortical plasticity in the transplant recipients, deletion of the receptors from the donor PV interneurons does not. Altogether, our results indicate that transplanted embryonic interneurons reactivate cortical plasticity by rejuvenating the function of host PV interneurons.

Highlights

The adult brain lacks sensitivity to changes in the sensory environment found in the juvenile brain
These results suggest that interneuron transplantation reactivates neuregulin 1 (NRG1)/ErbB4, a signaling pathway normally involved in developmental cortical plasticity, within the adult host PV interneurons and enables a second critical period
Previous studies have shown that visual deprivation rapidly decreases the responses of PV interneurons, and a series of in vitro experiments shows that the reduction can be prevented by treating PV interneurons with exogenous NRG111

Summary

Introduction

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. During the development of the visual cortex, the experiencedependent plasticity of excitatory circuits is gated by neuregulin 1 (NRG1)/ErbB4-dependent changes within parvalbumin (PV) GABAergic interneurons[9,10,11]. The level of NRG1 within PV interneurons peaks during the early juvenile development but gradually decreases as the cortex matures[11,15] These results suggest that NRG1/ErbB4 signaling may be involved in juvenile cortical plasticity. We show that NRG1/ErbB4 signaling is essential for transplant-reactivated cortical plasticity, and it depends on the ErbB4 receptor activity in the host but not the transplanted PV interneurons. Immunostaining revealed that >80% of these transplanted cells were PV+ (Supplementary Fig. 1c–e, g)

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