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Discovery of functional cell types in the inferior colliculus with combined molecular-genetic and electrophysiological approaches

结合分子遗传学和电生理学方法发现下丘功能细胞类型

基本信息

批准号：
9300564
负责人：
Nace L Golding
金额：
$ 18.97万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9300564
关键词：
Address Affect Anatomy Area Auditory Brain Calcium-Binding Proteins Cell Nucleus Cells Cellular Morphology Cereals Characteristics Classification Communication impairment Complement Cues Data Electrophysiology (science)Elements Exhibits Fluorescence Foundations Future Genetic Genetic Techniques Gerbils Goals Inferior Colliculus Interneurons Label Light Lighting Location Maps Mediating Midbrain structure Molecular Genetics Morphology Nature Neurons Pathway interactions Pattern Phenotype Physiological Physiology Population Property Proteins Recombinant adeno-associated virus (rAAV)Role Slice Stream Structure Synapses Testing Tinnitus Training Activity Viral Virus Whole-Cell Recordings auditory pathway auditory thalamus calbindin calbindin-D28K cell type excitatory neuron experimental study genetic approach hearing impairment in vivo inhibitory neuron intersectionality neural circuit neurochemistry novel optogenetics patch clamp promoter sound tool

项目摘要

Project Summary The central nucleus of the inferior colliculus (ICC) is a midbrain nucleus that serves as a pivotal point of convergence for a large number of ascending and descending auditory pathways. Understanding how computations carried out in the ICC relate to the underlying circuitry has been unusually difficult, in large part due to the lack of clear definitions of cell types. Indeed, there appears to be no correlations between intrinsic firing properties and cell morphology, even across excitatory and inhibitory cells. We propose that functionally distinct classes of neurons in the ICC can be identified and genetically accessed using viruses with promoters to different neurochemical markers. To address this hypothesis, we will combine electrophysiological and anatomical approaches with interdependent recombinant adeno-associated viruses (rAAV) targeting excitatory and inhibitory classes of calbindin D-28k ICC neurons (CB-excitatory and CB- inhibitory). CB is a calcium binding protein expressed in subsets of neurons of the ICC and in many other brain areas. Our preliminary results show that viruses carrying a CB promoter element target ICC neurons that exhibit a single firing phenotype, and that these neurons may comprise both excitatory and inhibitory subclasses. In Aim 1, we will combine in vivo labeling of ICC neurons with rAAV viruses, fluorescence guided patch recordings in IC slices, and anatomical analyses to fully characterize the two pools of CB neurons, including their physiology, morphology and axonal projections. In parallel, labeled neurons will be characterized according to their complement of expressed neurochemical markers. In Aim 2, we will use our molecular-genetic tools to drive channelrhodopsin-2 selectively in CB-excitatory or CB-inhibitory neurons. We will use structured illumination to map CB neurons' local inputs and targets in the ICC as well as to facilitate paired whole-cell patch recordings from connected neuron pairs, enabling characterization of synaptic properties between physiologically identified network partners. These experiments will serve as a blueprint for identifying and characterizing other functionally distinct circuits in the ICC. Our goal is to establish a foundation for future studies involving cell-specific optogenetic manipulations in vivo, where we can assess the roles of CB neurons and other defined ICC cell types in auditory computations.

项目总结