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Molecular Genetics of Visual Circuit Assembly in the Developing Superior Colliculus

发育中丘视觉电路组装的分子遗传学

基本信息

批准号：
10480753
负责人：
In-Jung Kim
金额：
$ 40.41万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10480753
关键词：
Affect Area Axon Behavior Behavioral Binding Brain Candidate Disease Gene Cells Cues Development Dorsal ETV1 gene Event Fright Functional disorder Genes Goals Knock-out Label Lateral Geniculate Body Lateral posterior nucleus of thalamus Maintenance Mediating Midbrain structure Molecular Molecular Genetics Motor Mus Mutant Strains Mice Neurologic Neurons Neurophysiology - biologic function Orphan Output Pathway interactions Pattern Phenocopy Phenotype Play Reaction Regulation Reporting Retina Retinoids Role Sensory Stimulus Structure Testing Thalamic Nuclei Thalamic structure Time Visual Visual impairment Wild Type Mouse base behavioral response brain circuitry cadherin-6 contactin experience experimental study genetic approach improved innovation insight loss of function mutant nervous system disorder neural circuit novel overexpression receptor response screening sensory input success superior colliculus Corpora quadrigemina transcription factor transcriptome sequencing visual stimulus

项目摘要

My long-term goal is to understand how neural circuits underlying specific brain functions are formed, modified by experience, and altered in neurological conditions. The goal of this proposal is to examine mechanisms that regulate formation of the long-range neuronal connections between the superior colliculus (SC) and specific subcortical brain areas. We chose to focus on the connections between superficial layer of SC (sSC) and the thalamus. The SC is a midbrain center that plays an important role in sensory and motor processing. The sSC receives visual inputs from the retina and cortex, and sSC-thalamic connections are known to mediate defensive responses to threating visual stimuli. As most of traditional studies have investigated organization of sensory inputs to sSC, little is known about mechanisms regulating development of sSC output pathways. Moreover, no study has described developmental regulation of sSC-thalamic circuits underlying visually-driven behavioral responses. In a screen for the markers labeling subsets of sSC neurons, we have identified several genes that are likely to control development of sSC neurons. Now, we propose to investigate the role of those molecules in sSC output circuit assembly. We have already demonstrated that a transcriptional factor, retinoid-related orphan receptor β (Rorβ), regulates sSC neuronal projections to specific thalamic nuclei. Here, we plan to examine downstream mechanisms of Rorβ-dependent regulation by gain- and loss-of-function approaches. We will also investigate the role of another transcription factor, Brn3b, in the development of distinct sSC circuits and identify the downstream effectors of Brn3b. Given that sSC neurons, confined to specific sublayers, selectively project axons to distinct thalamic nuclei, and that Brn3b and Rorβ are expressed in different sublayers of sSC, we hypothesize that Brn3b regulates axonal projections via Rorβ-independent mechanisms. Manipulations of Rorβ and Brn3b expression produce different patterns of altered axonal projections to the thalamic nucleus, known to govern visual-cue triggered behaviors. Based on these findings, we will test if Rorβ- and Brn3b-dependent mechanisms of circuit assembly are required for appropriate behavioral responses to visual threat. The success of the proposed project will improve our understanding of the molecular basis for establishing the long-range connections between sSC and thalamic areas. It will also provide novel mechanistic insights into developmental assmebly of subcortical visual circuits regulating responses to the threatening stimuli.

我的长期目标是了解特定大脑功能背后的神经回路是如何形成和修改的