Modulation of dendritic spiking in vivo

 描述(由申请人提供)：皮层活动受到严格调控以支持适应性行为，但这种调控背后的机制尚不清楚。在这个项目中，我们将研究皮层活动是如何在体内调节的，直接在突触输入部位，树突通过电压门控离子通道和NMDA受体主动处理突触输入。我们最近发现，这些机制支持清醒小鼠的树突状尖峰。这些树突棘波以去极化的形式传播到胞体，可以触发常规的轴突棘波，从而代表了一层有助于神经元选择性的计算处理。最近阐明的一个涉及神经调节和树突靶向中间神经元的电路基序可能在调节感觉加工和行为过程中的树突尖峰起关键作用。在这里，我们使用树突状膜片钳记录、光遗传学和新的多光子成像技术来询问这个电路基序，它对树突尖峰的影响，以及它在感觉处理和行为过程中的活动。由于树突棘波是皮层回路中突触整合的重要组成部分，而功能障碍的突触整合与复杂的精神和神经疾病有关，因此该项目的结果最终可能有助于新的治疗策略。

 DESCRIPTION (provided by applicant): Cortical activity is tightly regulated to support adaptive behavior, but the mechanisms underlying this regulation are unclear. In this project, we will investigate how cortical activity is regulated in vivo, directly at the site of synaptic input Dendrites actively process synaptic input using voltage-gated ion channels and NMDA receptors. We recently showed that these mechanisms support dendritic spiking in awake mice. These dendritic spikes propagate to the soma as depolarizations that can trigger conventional axonal spikes, and thus represent a layer of computational processing that contributes to neuronal selectivity. A recently elucidated circuit motif involving neuromodulation and dendrite-targeting interneurons could play a key role in regulating dendritic spiking during sensory processing and behavior. Here, we use dendritic patch clamp recordings, optogenetics, and new multiphoton imaging technology to interrogate this circuit motif, its effects on dendritic spiking, and its activity during sensory processing and behavior. Since dendritic spiking is an essential component of synaptic integration in cortical circuitry, and dysfunctional synaptic integration is implicated in complex psychiatric and neurological disorders, results from this project can eventually contribute to new therapeutic strategies.