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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：
10244937
负责人：
Carolyn Gray Sweeney
金额：
$ 7.11万
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/10244937
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 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 rabies viral tracing 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.

项目摘要听觉感知学习诱导听觉皮层（A1）的可塑性，可以改善听觉感知，但引发这些变化的神经机制尚不清楚。穿过感觉皮层区域，抑制中间神经元正在成为可塑性的“守门人”--调节神经元之间严格控制的平衡，兴奋和抑制。皮质中间神经元群体由许多细胞亚型组成通过形态学，生理学和连接性来区分，这表明有几种不同的回路，可塑性调节这些特定的中间神经元回路如何促进皮层可塑性和感觉学习仍然知之甚少。最近的研究表明，抑制性中间神经元内的表层A1促进听觉可塑性。这些中间神经元的特征在于5-羟色胺受体5 HT 3A-R的表达，并且对5-羟色胺受体5 HT 3A-R的表达有反应。乙酰胆碱虽然许多研究都集中在A1可塑性中乙酰胆碱信号的作用，但很少有研究表明， 5-羟色胺的功能该提议集中于表面5 HT 3A-R中间神经元的子集表达血管活性肠肽（VIP），这是一个有前途的目标，调节可塑性在成人A1。这些研究将验证向VIP中间神经元传递的5-羟色胺信号促进小鼠大脑可塑性的假设。 A1在听觉知觉学习期间。首先，电路追踪技术将用于识别血清素- 在A1中表达与VIP中间神经元突触的神经元。第二，体内双光子成像将确定在声音辨别过程中，A1中的VIP能终末和VIP中间神经元何时被募集学习这些研究将1）确定以前未表征的5-羟色胺神经元到VIP中间神经元回路，和2）将确定在VIP中间神经元中5-羟色胺信号传导的变化是否是A1可塑性的基础。听觉知觉学习这项研究的结果可能会为发现新的疗法，利用特定的皮层回路，以促进成人的可塑性。