Mardinly A R, Spiegel I, Patrizi A, Centofante E, Bazinet J E, Tzeng C P, Mandel-Brehm C, Harmin D A, Adesnik H, Fagiolini M, Greenberg M E
Department of Molecular and Cellular Biology, University of California Berkeley, 205 Life Sciences Addition, Berkeley, California 94720, USA.
Department of Neurobiology, Harvard Medical School, 220 Longwood Ave, Boston, Massachusetts 02115, USA.
Nature. 2016 Mar 17;531(7594):371-5. doi: 10.1038/nature17187. Epub 2016 Mar 9.
Inhibitory neurons regulate the adaptation of neural circuits to sensory experience, but the molecular mechanisms by which experience controls the connectivity between different types of inhibitory neuron to regulate cortical plasticity are largely unknown. Here we show that exposure of dark-housed mice to light induces a gene program in cortical vasoactive intestinal peptide (VIP)-expressing neurons that is markedly distinct from that induced in excitatory neurons and other subtypes of inhibitory neuron. We identify Igf1 as one of several activity-regulated genes that are specific to VIP neurons, and demonstrate that IGF1 functions cell-autonomously in VIP neurons to increase inhibitory synaptic input onto these neurons. Our findings further suggest that in cortical VIP neurons, experience-dependent gene transcription regulates visual acuity by activating the expression of IGF1, thus promoting the inhibition of disinhibitory neurons and affecting inhibition onto cortical pyramidal neurons.
抑制性神经元调节神经回路对感觉经验的适应,但经验控制不同类型抑制性神经元之间的连接以调节皮质可塑性的分子机制在很大程度上尚不清楚。在这里,我们表明,将饲养在黑暗环境中的小鼠暴露于光线下,会在皮质中表达血管活性肠肽(VIP)的神经元中诱导出一个基因程序,该程序与在兴奋性神经元和其他抑制性神经元亚型中诱导出的程序明显不同。我们确定Igf1是VIP神经元特有的几个活性调节基因之一,并证明IGF1在VIP神经元中自主发挥作用,增加对这些神经元的抑制性突触输入。我们的研究结果进一步表明,在皮质VIP神经元中,依赖经验的基因转录通过激活IGF1的表达来调节视敏度,从而促进对去抑制神经元的抑制,并影响对皮质锥体神经元的抑制。