Emergence of somatostatin interneuron function in the developing visual cortex

项目总结： GABA能中间神经元是新皮质环路正常发育和功能的中枢。在……里面 特别是，表达生长抑素(SST-INS)的细胞被认为在这两种情况下都起着关键作用 自发的和感觉诱发的神经元活动，主要是通过它们对树突的强烈抑制 兴奋性锥体神经元。然而，尽管皮质SST-ins在成年动物中的作用一直很好 特征是，它们在发育皮质回路中的功能尚不清楚。事实上，职能部门的组织 SST-INS在不同发育时间点的连通性尚不清楚。我们的初步数据显示 令人惊讶的发现是，SST-INS在幼年小鼠的眼睛睁开时还不存在电路水平的影响， 潜在地揭示了这些中间神经元和它们的影响的关键发展轨迹 对视觉处理的贡献。为了进一步探讨这一观察结果，我们建议结合一些 方法学方法，包括青少年病毒注射、高级行为状态分析、光遗传学 操纵，以及神经元信号的双光子监测。我们将检验以下假设：(1) SST-INS的视觉响应特性的发展直接影响到局部和大型海洋的发展。 在出生后阶段测量大脑皮层回路。(2)这些电路的成熟有助于 自发性活动和视觉诱发活动的状态依赖性调节的发育性出现 视觉皮质。我们的结果将为我们提供前所未有的洞察力，了解 SST-ins及其与大脑皮层视觉加工的关系。

PROJECT SUMMARY: GABAergic interneurons are central to the normal development and function of neocortical circuits. In particular, cells that express the peptide somatostatin (SST-INs) are thought to play critical roles in both spontaneous and sensory-evoked neuronal activity, primarily via their robust inhibition of the dendrites of excitatory pyramidal neurons. However, whereas the role of cortical SST-INs in adult animals has been well characterized, their function in developing cortical circuits is unknown. Indeed, the organization of functional connectivity of SST-INs at various developmental time points remains unexplored. Our preliminary data suggest the surprising finding that the circuit-level influence of SST-INs is not yet present at eye opening in juvenile mice, potentially revealing a critical developmental trajectory for the influence of these interneurons and their contribution to visual processing. To further explore this observation, we propose to combine a number of methodological approaches, including juvenile viral injection, advanced behavioral state analysis, optogenetic manipulations, and 2-photon monitoring of neuronal signaling. We will test the following hypotheses: (1) The development of the visual response properties of SST-INs directly influences the development of local and large- scale cortical circuits during the postnatal period. (2) The maturation of these circuits contributes to the developmental emergence of state-dependent modulation of spontaneous and visually evoked activity in the visual cortex. Our results will provide an unprecedented level of insight into the development and function of SST-INs and their relationship to visual processing in the neocortex.