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

两个第 1 层中间神经元群对听觉皮层的差异控制

• 批准号: 10531214
• 负责人: ANNE E TAKESIAN
• 金额: $ 51.21万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10531214
• 关键词: Acoustics; Acute; Address; Adult; Anatomy; Auditory; Auditory area; Axon; Behavior; Behavioral; Brain; Brain region; Calcium; Cells; Communication impairment; Complex; Data; Development; Electrophysiology (science); Environment; Genetic Transcription; Hearing problem; Image; In Vitro; Interneurons; Laboratories; Learning; Life; Locomotion; Maps; Measures; Medial geniculate body; Mediating; Modality; Monitor; Mus; Neuromodulator; Neuronal Plasticity; Neurons; Outcome; Output; Pathway interactions; Pattern; Perceptual learning; Peripheral; Population; Property; Rabies; Recovery; Research; Rewards; Sensory; Signal Transduction; Site; Slice; Stimulus; Synapses; System; Techniques; Technology; Thalamic structure; Vasoactive Intestinal Peptide; Viral; Work; auditory thalamus; brain cell; cell type; cholinergic; experience; experimental study; hearing impairment; in vivo; neuronal circuitry; neuroregulation; neurotrophic factor; novel therapeutic intervention; optogenetics; postsynaptic; presynaptic; receptor; recruit; reinforcer; response; sensory cortex; sensory input; sound; two-photon; vigilance

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.

项目摘要。初级听觉皮层（A1）是一个中央站点的收敛，为上升的感觉 投射和来自不同神经调节区域的投射。这些输入在A1中相互作用， 每时每刻的皮层活动，并驱动突触连接的持久变化， 听觉行为学习我们最近的研究表明，在神经元中存在一组不同的抑制性中间神经元。 皮质层1（L1）具有整合来自听觉丘脑的调谐感觉输入的特权能力， 来自胆碱能和多巴胺能脑区的神经调节输入。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靶点，有力地控制皮层网络活动， 可塑性我们最近的研究结果表明，两种不同类型的L1中间神经元定义的表达， 神经源性神经营养因子（NDNF）或血管活性肠肽（VIP）可接受不同的 输入并向其皮层目标发送不同的输出。我们建议每个L1中间神经元类都有一个 在控制皮层活动和可塑性方面有特殊的功能。然而，NDNF和 VIP L1中间神经元亚型被激活并控制皮质状态和可塑性尚未完全了解。到 为了解决这个未知问题，我们将使用解剖学、跨突触病毒追踪和电生理学方法 阐明小鼠A1区神经营养因子和VIP L1中间神经元的突触前和突触后伴侣。我们还将使用 在行为小鼠中进行双光子成像以确定NDNF和VIP L1的体内活性和可塑性 interneurons中间neurons神经元during期间auditory听觉perceptual知觉learning学习.这项研究的结果将确定L1电路机制 这可以促进成年人的听觉可塑性，并可用于推进听力损失后的治疗。