Modulation of dendritic spiking in vivo

 描述（由申请人提供）：皮质活动受到严格调节，以支持适应性行为，但这种调节的机制尚不清楚。在这个项目中，我们将研究如何在体内调节皮层活动，直接在突触输入的网站树突积极处理突触输入使用电压门控离子通道和NMDA受体。我们最近发现，这些机制支持清醒小鼠的树突棘。这些树突棘波传播到索马作为去极化，可以触发传统的轴突棘波，因此代表了一层计算处理，有助于神经元的选择性。最近阐明的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处理和行为过程中的树突尖峰发挥关键作用。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，其对树突尖峰的影响，以及其在感觉处理和行为过程中的活性。由于树突棘波是皮质回路中突触整合的重要组成部分，而功能失调的突触整合与复杂的精神和神经系统疾病有关，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.