Cellular mechanisms of GABAergic inhibition in neocortical dendrites

项目摘要 大脑皮层兴奋性和抑制性回路的发展对 建立正常的大脑活动模式，以及这一过程的失调可能有助于 一些神经精神障碍，包括精神分裂症和自闭症。然而， 早期发育中抑制性突触发生的组织和调控仍然很差 明白了。这种知识的缺乏，部分是由于GABA能电路和 缺乏适当的工具来剖析不同IN人群对 早期的GABA能信号。在本研究中，我们利用电生理学的组合， GABA能突触的光遗传学、双光子成像和去化以及荧光标记 目的：(1)阐述锥体神经元(PN)功能抑制传入的发展 树突，(2)揭示了电路特异性GABA能可塑性的新机制，以及(3) 阐明谷氨酸和γ-氨基丁酸能信号在神经细胞正常连接中的相互作用 大脑皮层回路。我们的总体目标是了解兴奋性和抑制性之间的联系 在发育过程中运行并维持皮质回路功能的信号。我们期待着 我们的结果将为探索GABA能功能的细胞生物学提供新的途径 以及大脑发展和适应经验的一般机制。

Project Summary The development of excitatory and inhibitory circuits in the neocortex is critical for establishing normal patterns of brain activity, and dysregulation of this process may contribute to a number of neuropsychiatric disorders, including schizophrenia and autism. However, the organization and regulation of inhibitory synaptogenesis during early development remain poorly understood. This lack of knowledge is due, in part, to heterogeneity in GABAergic circuits and the absence of appropriate tools for dissecting the contribution of different IN populations to early GABAergic signaling. In the present study, we utilize a combination to electrophysiology, optogenetics, 2-photon imaging and uncaging, and fluorescent labeling of GABAergic synapses to (1) elaborate the development of functional inhibitory inputs to pyramidal neuron (PN) dendrites, (2) reveal novel mechanisms for circuit-specific GABAergic plasticity, and (3) elucidate the interactions of glutamatergic and GABAergic signaling in the normal wiring of cortical circuits. Our overall goal is to understand the links between excitatory and inhibitory signaling that operate during development and maintain cortical circuit function. We expect that our results will generate new avenues for exploring both the cell biology of GABAergic function and the general mechanisms by which the brain develops and adapts to experience.