Modulation of adult-born neuron excitability by coupling to GABAergic networks
Modulation of adult-born neuron excitability by coupling to GABAergic networks
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DOI：
10.1101/598615
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发表时间：
2019-04
期刊：
影响因子：
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通讯作者：
S. M. Yang;A. I. Groisman;A. F. Schinder
中科院分区：
文献类型：
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作者：
S. M. Yang;A. I. Groisman;A. F. Schinder
包括人类在内的成年哺乳动物的海马区产生新的颗粒细胞(GC)。这些神经元生长在一个由抑制控制的相当安静的网络中，但它们最初是过度兴奋的，因为它们与占主导地位的GABA能音调分离。控制新GC兴奋性的确切时间和突触机制仍不清楚。为了建立准确的神经发生介导的回路重塑的基质，我们研究了发育中的GC和两种主要类型的GABA能中间神经元-小白蛋白(PV-INS)和生长抑素表达细胞(SST-INS)之间的传入和传出突触发生。来自PV-INS的输入以胞体为靶点，并在4周大的GCs中突然生长，与它们高度兴奋的时期的终止一致。相反，来自SST-IN的输入是树枝状的，并稳定发展，直到8周达到成熟。从GCs到PV-INS和SST-INS的输出突触发生中也显示了这些突触成熟的阶梯和分级模式。成熟时，GC的活动由以PV-IN为主的前馈环路和包括这两种IN类型的反馈环路控制。因此，新队列到抑制网络的延迟整合产生了异质神经元群体，这有助于提高齿状回的反应动态范围。
New granule cells (GCs) are generated in the hippocampus of adult mammals including humans. These neurons grow in a rather silent network governed by inhibition, but they are initially hyperexcitable because they are uncoupled from the dominant GABAergic tone. The precise timing and synaptic mechanisms that control the excitability of new GCs remain unclear. To build an accurate matrix of neurogenesis-mediated circuit remodeling, we studied afferent and efferent synaptogenesis between developing GCs and two major types of GABAergic interneurons; parvalbumin-(PV-INs) and somatostatin-expressing cells (SST-INs). Inputs from PV-INs targeted the soma and grew abruptly in >4-week-old GCs, coincident with the termination of their highly excitable period. In contrast, inputs from SST-INs were dendritic and developed steadily until reaching maturity by 8 weeks. These step-wise vs. graded patterns of synaptic maturation were also revealed in output synaptogenesis from GCs onto PV-INs and SST-INs. When mature, activity of GCs becomes controlled by feedforward loops dominated by PV-INs, and feedback loops that include both IN types. Therefore, the delayed integration of new cohorts into inhibitory networks generates heterogeneous neuronal populations that contribute to enhance the dynamic range of responsiveness in the dentate gyrus.