Emergence of somatostatin interneuron function in the developing visual cortex

项目概要： GABA能中间神经元对新皮层回路的正常发育和功能至关重要。在 特别是，表达肽生长抑素（SST-INs）的细胞被认为在这两个过程中起着关键作用。 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， 虽然它们的特性，但它们在发展皮层回路中的功能尚不清楚。实际上，组织职能 在不同发育时间点的SST-INs的连接性仍然未被探索。我们的初步数据显示 令人惊讶的发现是，在幼年小鼠睁眼时，SST-IN的回路水平影响还不存在， 这可能揭示了这些中间神经元及其 对视觉处理的贡献。为了进一步探索这一观察结果，我们建议将联合收割机结合一些 方法学方法，包括青少年病毒注射，先进的行为状态分析，光遗传学 操纵和神经元信号的双光子监测。我们将测试以下假设：（1） SST-INs视觉反应特性的发展直接影响局部和大- 在出生后的这段时间里，(2)这些回路的成熟有助于 自发和视觉诱发活动的状态依赖性调制的发展出现， 视觉皮层我们的研究结果将提供一个前所未有的水平洞察的发展和功能， SST-INs及其与新皮层视觉处理的关系

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.