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：
10402662
负责人：
Carolyn Gray Sweeney
金额：
$ 0.25万
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 2022-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10402662
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.

项目概要听觉感知学习会诱导听觉皮层 (A1) 的可塑性，从而改善听觉感知，但触发这些变化的神经机制尚不清楚。中间神经元正在成为可塑性的“看门人”——调节严格控制的平衡皮质中间神经元群由许多细胞亚型组成。通过形态学、生理学和连接性来区分，这表明存在几种不同的电路可塑性调节。这些特定的中间神经元回路如何促进皮质可塑性和感觉学习仍然知之甚少。最近的研究表明，A1 浅层内的抑制性中间神经元可促进听觉可塑性。这些中间神经元的特征是表达血清素受体 5HT3A-R，并对虽然多项研究都集中在乙酰胆碱信号传导在 A1 可塑性中的作用，但很少有研究关注。已知血清素的功能。该提案重点关注表面 5HT3A-R 中间神经元的子集。表达血管活性肠肽 (VIP)，这是调节成人 A1 可塑性的有希望的靶标。这些研究将检验以下假设：向 VIP 中间神经元发送血清素信号可促进小鼠的可塑性 A1 在听觉感知学习过程中，首先，将使用电路追踪技术来识别血清素。其次，体内双光子成像将突触到 A1 中的 VIP 中间神经元上。确定 A1 中的血清素末梢和 VIP 中间神经元在声音辨别过程中何时被招募这些研究将 1) 识别先前未表征的血清素神经元到 VIP 中间神经元回路， 2) 将确定 VIP 中间神经元的血清素信号变化是否是 A1 可塑性的基础这项研究的结果可能会为听觉感知学习的发现开辟新的视野。利用特定皮质回路来促进成人可塑性的新疗法。