Rajkovich Kacey E, Loerwald Kristofer W, Hale Carly F, Hess Carolyn T, Gibson Jay R, Huber Kimberly M
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Neuron. 2017 Jan 4;93(1):48-56. doi: 10.1016/j.neuron.2016.11.022. Epub 2016 Dec 15.
Development of proper cortical circuits requires an interaction of sensory experience and genetic programs. Little is known of how experience and specific transcription factors interact to determine the development of specific neocortical circuits. Here, we demonstrate that the activity-dependent transcription factor, Myocyte enhancer factor-2C (Mef2c), differentially regulates development of local versus long-range excitatory synaptic inputs onto layer 2/3 neurons in the somatosensory neocortex in vivo. Postnatal, postsynaptic deletion of Mef2c in a sparse population of L2/3 neurons suppressed development of excitatory synaptic connections from all local input pathways tested. In the same cell population, Mef2c deletion promoted the strength of excitatory inputs originating from contralateral neocortex. Both the synapse promoting and synapse suppressing effects of Mef2c deletion required normal whisking experience. These results reveal a role of Mef2c in experience-dependent development of specific sensory neocortical circuits.
适当的皮质回路发育需要感觉经验和基因程序的相互作用。关于经验和特定转录因子如何相互作用以决定特定新皮质回路的发育，我们所知甚少。在这里，我们证明了活性依赖的转录因子，肌细胞增强因子2C（Mef2c），在体内对体感新皮质第2/3层神经元上的局部与长程兴奋性突触输入的发育具有不同的调节作用。出生后，在稀疏的第2/3层神经元群体中进行Mef2c的突触后缺失，抑制了来自所有测试的局部输入通路的兴奋性突触连接的发育。在相同的细胞群体中，Mef2c的缺失增强了源自对侧新皮质的兴奋性输入的强度。Mef2c缺失的突触促进和突触抑制作用都需要正常的触须体验。这些结果揭示了Mef2c在特定感觉新皮质回路的经验依赖性发育中的作用。
