Differential Control of Auditory Cortex by Two Populations of Layer 1 Interneurons

项目摘要。初级听觉皮质(A1)是上行感觉的中心会聚部位 来自不同神经调节区的投射和投射。这些输入在A1中相互作用，以影响 瞬间的皮质活动并驱动突触连接的长期变化，这可能是基础 听觉行为学习。我们最近的工作揭示了脑内一组不同的抑制性中间神经元 皮层1(L1)具有整合来自听觉丘脑的调谐感觉输入和 胆碱能和5-羟色胺能脑区的神经调节性输入。这些L1中间神经元在空间上发送- 精确的轴突投射到突触后目标，有力地控制皮质网络活动和 可塑性。我们最近的结果表明，两类不同类型的L1中间神经元定义为 神经源性神经营养因子(NDNF)和血管活性肠肽(VIP)可能受到不同的影响 输入并将不同的输出发送到它们的皮质目标。我们提出每个L1中间神经元类都有一个 在控制皮质活动和可塑性方面的特殊作用。然而，NDNF和NDNF的机制 VIP L1中间神经元亚型被激活，控制皮质状态和可塑性尚不完全清楚。至 为了解决这一未知问题，我们将使用解剖学、跨突触病毒追踪和电生理方法 目的：阐明小鼠A1区NDNF和VIP L1中间神经元突触前和突触后的配对。我们还将使用 双光子成像检测NDNF和VIP L1的体内活性和可塑性 听觉知觉学习中的中间神经元。这项研究的结果将确定L1电路机制 促进成年后的听觉可塑性，并可用于推进听力损失后的治疗。

Project Summary. The primary auditory cortex (A1) is a central site of convergence for ascending sensory projections and projections from diverse neuromodulatory regions. These inputs interact in A1 to both influence moment-to-moment cortical activity and drive long-lasting changes in synaptic connections that may underlie auditory behavioral learning. Our recent work has revealed that a diverse group of inhibitory interneurons in cortical layer 1 (L1) has a privileged capacity to integrate tuned sensory input from the auditory thalamus and neuromodulatory inputs from cholinergic and serotonergic brain regions. These L1 interneurons send spatially- precise axonal projections to their postsynaptic targets that powerfully control cortical network activity and plasticity. Our recent results suggest that two distinct classes of L1 interneurons defined by the expression of either neuron-derived neurotrophic factor (NDNF) or vasoactive intestinal peptide (VIP) may receive differential inputs and send distinct outputs to their cortical targets. We propose that each L1 interneuron class has a specialized function in controlling cortical activity and plasticity. However, the mechanisms by which NDNF and VIP L1 interneuron subtypes are activated and control cortical state and plasticity are not fully understood. To address this unknown, we will use anatomical, trans-synaptic viral tracing, and electrophysiological approaches to elucidate the pre and post-synaptic partners of NDNF and VIP L1 interneurons in mouse A1. We will also use two-photon imaging in behaving mice to determine the in vivo activity and plasticity of NDNF and VIP L1 interneurons during auditory perceptual learning. The results of this research will identify L1 circuit mechanisms that promote auditory plasticity in adulthood and can be exploited to advance treatments following hearing loss.