Impact of local network dynamics on visual cortex function

项目摘要 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，不同类别的SST-INs在深层的功能作用 皮质层仍然未知。此外，尽管SST-INs在大脑皮层浅层的作用， 成年动物的特征已经很好地描述了，但它们在发育皮层回路中的功能尚不清楚。的确， 在不同发育时间点，SST-神经元突触连接的组织仍然存在， 未开发的我们的初步数据表明了一个令人惊讶的发现，即SST-IN的电路水平影响是 尚未出现在幼年小鼠的眼睛睁开，可能揭示了一个关键的发展轨迹， 这些中间神经元的影响及其对视觉处理的贡献。为了进一步探讨这一点， 观察，我们建议结合联合收割机的方法，包括光遗传学 操纵，神经元信号的双光子和电生理监测，以及体内 药理学操作。我们将检验以下假设：（1）SST-IN的广泛输入 它们对局部和大规模皮质回路的影响在产后期间发展。(2)SST-IN 视觉皮层浅层和深层的群体在功能上是不同的，并且受到不同的调节 行为状态。(3)SST-INs的活性及其潜在的兴奋性和神经调节性突触 驾驶员受发育年龄的强烈调节。我们的成果将提供前所未有的 深入了解SST-INs的发展和功能及其与视觉加工的关系， 新皮层

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.