Impact of local network dynamics on visual cortex function

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，不同类别的SST-IN在深部 皮质层仍然未知。此外，鉴于SST-ins在大脑皮层浅层的作用 成年动物已经有了很好的特征，它们在大脑皮质环路发育中的功能尚不清楚。的确， SST-ins在不同发育时间点的突触连接组织仍然存在 未被开发的。我们的初步数据表明，令人惊讶的发现是，SST-INS在电路级的影响是 还没有出现在幼年小鼠的眼睛睁开时，可能揭示了 这些中间神经元的影响及其在视觉加工中的作用。为了进一步探索这一点 观察，我们建议结合一些方法学方法，包括光遗传学 神经信号的操纵、双光子和电生理监测，以及体内 药理操控。我们将检验以下假设：(1)SST-INS的广泛输入 它们对局部和大规模皮质环路的影响发生在出生后时期。(2)SST-IN 视皮层浅层和深层的群体在功能上是不同的，并有不同的调节 通过行为状态。(3)SST-ins的活性及其兴奋性和神经调节性突触 驾车者受到发育年龄的严格控制。我们的结果将提供前所未有的水平 洞察SST-INS的发展和功能及其与视觉加工的关系 大脑皮层。

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, the functional roles of the diverse classes of SST-INs in deep cortical layers remain unknown. Furthermore, whereas the role of SST-INs in superficial cortical layers of adult animals has been well characterized, their function in developing cortical circuits is unknown. Indeed, the organization of synaptic 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 optogenetic manipulations, 2-photon and electrophysiological monitoring of neuronal signaling, and in vivo pharmacological manipulations. We will test the following hypotheses: (1) The extensive inputs to SST-INs and their influence on local and large-scale cortical circuits develop during the postnatal period. (2) SST-IN populations in superficial and deep layers of visual cortex are functionally distinct and differentially regulated by behavioral state. (3) The activity of SST-INs and their underlying excitatory and neuromodulatory synaptic drivers are strongly regulated by developmental age. 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.