Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, 92697-2715, USA.
Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, 92697-2715, USA.
Nat Commun. 2021 Feb 8;12(1):862. doi: 10.1038/s41467-021-21097-4.
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.
成年大脑对幼年大脑中发现的感觉环境变化不敏感。已经证明，胚胎中间神经元的移植可以使成年宿主视觉皮层恢复幼年时期的可塑性。目前还不清楚移植的中间神经元是否直接介导了皮质可塑性的恢复，或者这些细胞是否通过改变宿主中间神经元回路间接起作用。在这里，我们发现移植诱导的小鼠宿主回路的重组是由宿主 PV 中间神经元中的神经调节蛋白 1（NRG1）/表皮生长因子受体 4（ErbB4）信号特异性介导的。短暂的视觉剥夺会降低宿主 PV 中间神经元的视觉活动，但对移植的 PV 中间神经元的反应几乎没有影响。外源性 NRG1 既可以防止视觉剥夺引起的宿主 PV 中间神经元视觉反应的减少，也可以阻止移植诱导的宿主回路重组。虽然从宿主 PV 中间神经元中删除 ErbB4 受体可以阻止移植受体中的皮质可塑性，但从供体 PV 中间神经元中删除受体则不会。总之，我们的研究结果表明，移植的胚胎中间神经元通过恢复宿主 PV 中间神经元的功能重新激活了皮质可塑性。
