Serotonin Regulation of VIP Interneurons and Auditory Learning

VIP 中间神经元的血清素调节和听觉学习

基本信息

批准号：
10011558
负责人：
Carolyn Gray Sweeney
金额：
$ 6.53万
依托单位：
MASSACHUSETTS EYE AND EAR INFIRMARY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-30 至 2022-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10011558
关键词：
Acetylcholine Address Adult Anatomy Auditory Auditory Brain Stem Implants Auditory Perception Auditory area Axon Behavioral Brain Cells Cochlea Data Development Discrimination Learning Disinhibition Environment Equilibrium Future Glutamates Goals Hearing Hearing Aids In Situ Hybridization Interneurons Laboratories Lead Learning Life Locomotion Measures Mentors Molecular Morphology Mus Neuromodulator Neuronal Plasticity Neurons Optics Outcome Pathway interactions Perceptual learning Peripheral Physiology Population Presynaptic Terminals Rabies virus Recovery Regulation Research Rewards Role Scientist Sensory Serotonergic System Serotonin Signal Transduction Source Stimulus Structure Synapses Techniques Technology Testing Training Vasoactive Intestinal Peptide Viral Withdrawal Work career critical period experience experimental study gene therapy hearing impairment improved in vivo in vivo calcium imaging in vivo two-photon imaging neuromechanism neuronal circuitry neuroregulation novel novel strategies novel therapeutics raphe nuclei receptive field recruit sensory cortex serotonin receptor skills sound vigilance

项目摘要

Project Summary Auditory perceptual learning induces plasticity in the auditory cortex (A1) that can improve hearing perception, but the neural mechanisms that trigger these changes are unclear. Across sensory cortical regions, inhibitory interneurons are emerging as “gate keepers” to plasticity - regulating tightly controlled balances between excitation and inhibition. The cortical interneuron population is composed of numerous cell subtypes distinguished by morphology, physiology, and connectivity, suggesting that there are several distinct circuits for plasticity regulation. How these specific interneuron circuits contribute to cortical plasticity and sensory learning remains poorly understood. Recent work suggests that inhibitory interneurons within the superficial layers of A1 promote auditory plasticity. These interneurons are characterized by expression of the serotonin receptor, 5HT3A-R, and are responsive to acetylcholine. While multiple studies have focused on the role of acetylcholine signaling in A1 plasticity, little is known about the function of serotonin. This proposal focuses on a subset of superficial 5HT3A-R interneurons expressing vasoactive intestinal peptide (VIP) that are a promising target for regulating plasticity in adult A1. The studies will test the hypothesis that serotonin signaling to VIP interneurons promotes plasticity in mouse A1 during auditory perceptual learning. First, circuit tracing techniques will be used to identify the serotonin- expressing neurons that synapse onto VIP interneurons in A1. Second, in vivo two-photon imaging will determine when serotonergic terminals and VIP interneurons in A1 are recruited during sound discrimination learning. These studies will 1) identify a previously uncharacterized serotonin neuron to VIP interneuron circuit, and 2) will determine whether changes in serotonin signaling to VIP interneurons underlie A1 plasticity during auditory perceptual learning. The results of this research will likely open new horizons for the discovery of novel therapies that tap into specific cortical circuits to promote adult plasticity.

项目摘要听觉知觉学习会在听觉皮层（A1）中诱导可塑性，从而改善听力感知，但是触发这些变化的神经元机制尚不清楚。在感觉皮质区域，抑制性中间神经元正作为“门守门员”出现到可塑性 - 控制紧密控制的平衡兴奋和抑制。皮质间神经元种群由许多细胞亚型组成由形态学，生理和连通性区别，表明有几个不同的电路可塑性调节。这些特定的内神经元电路如何有助于皮质可塑性和感觉学习仍然很了解。最近的工作表明，A1浅层层中的抑制性神经元促进了听觉可塑性。这些中间神经元的特征在于5-ht3a-r的5-ht3a-r的表达，并且对虽然多项研究集中于乙酰胆碱信号在A1可塑性中的作用，但很少有关5-羟色胺的功能。该提案重点介绍了表面5HT3A-R INTERURONS的一部分表达血管活性肠肽（VIP），是调节成人A1可塑性的承诺靶标。研究将检验以下假设，即5-羟色胺信号传导对VIP中间神经元促进小鼠的可塑性听觉感知学习期间的A1。首先，电路追踪技术将用于识别血清素 - 表达突触到A1中VIP中间神经元的神经元。第二，体内两光子成像将确定在声音歧视期间募集A1中的血清素能终端和VIP中间神经元学习。这些研究将1）确定先前未表征的5-羟色胺神经元到VIP中间神经元电路， 2）将确定5-羟色胺信号传导对VIP中间神经元的变化是否是A1塑性的基础听觉感知学习。这项研究的结果可能会为发现新的疗法将特定的皮质圆圈促进成人可塑性。