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Neuroendocrine control of synaptic connectivity.

突触连接的神经内分泌控制。

基本信息

批准号：
10522227
负责人：
Hannes Erich Buelow
金额：
$ 51.21万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-15 至 2027-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10522227
关键词：
Adult Afferent Neurons Agonist Anatomy Animal Model Animals Attention Behavior Behavioral Behavioral Assay Beta Cell Bilateral Biological Models Biological Process Brain Brain imaging Caenorhabditis elegans Calcium Cells Cerebral Dominance Defect Development Electrons Environment Environmental Risk Factor Exhibits Exposure to Foundations Genetic Genetic Transcription Genetic study Goals Guanylate Cyclase Heart Hormonal Human Image Individual Insulin Insulin Receptor Ions Knock-out Label Language Left Link Liver Locomotion Measurable Mediating Mental Depression Mental disorders Microscopic Molecular Morphology Nematoda Neurons Neurosciences Neurosecretory Systems Organ Post-Traumatic Stress Disorders Psychology Research Resolution Role Schizophrenia Sensory Shapes Signal Pathway Sodium Chloride Space Perception Structure Sum Synapses Taste Buds Testing Time Transgenic Organisms Translating Translations Work antagonist autism spectrum disorder base behavioral study cognitive ability experience experimental study genetic manipulation hormonal signals imaging study insight insulin signaling neural circuit neural network neuropsychiatric disorder neuropsychiatry optogenetics programs receptor receptor expression receptor function reconstruction response visual processing

项目摘要

PI: Buelow, Hannes E. Project Summary The general body plan of most animals follows a bilateral symmetry. Some organs such as the heart and liver break this gross anatomical symmetry, while other structures such as the brain display a superficial bilaterally symmetric anatomy. Nonetheless, it has been known for a long time that the two hemispheres of the human brain serve distinct functions, and many classical examples in neuroscience and psychology have shown the importance of asymmetry in brain function. For example, higher order cognitive abilities such as language, spatial orientation, attention, and visual processing exhibit left-right (L-R) functional asymmetries in humans. Of note, many neuropsychiatric conditions including autism spectrum disorders, depression, schizophrenia, and post-traumatic stress disorder display defects in brain laterality, further underscoring the importance of lateralized brain function. Not surprisingly, neuropsychiatric conditions often have a genetic and, hence possibly, a developmental component. Most of these conditions are also influenced by environmental factors, yet how the environment interfaces with connectivity remains largely unknown. We have identified an asymmetric synaptic connection between two pairs of sensory neurons in the nematode Caenorhabditis elegans that changes in response to experience. Importantly, this connection is controlled cell-non- autonomously from other cells by insulin signaling, which in turn is regulated by experience. This provides a paradigm to investigate, on a molecular level and in single cell resolution, how the environment can change hardwiring of a neural circuit in an experience-dependent manner. The goal of this proposal is to investigate the developmental, plastic and functional aspects of this connection using C. elegans as a model system. In Specific Aim 1, we will determine the mechanisms by which experience changes connectivity. We will determine whether transcription or translation is required and whether neuronal activity is necessary and sufficient, and in which cells. In Specific Aim 2, we will determine the role of insulin signaling in controlling synaptic connectivity. Specifically, we will test which insulin-like agonists and antagonists function in which cells to effect the changes in connectivity; where the receptor functions and in which genetic context. Lastly, in Specific Aim 3, we will determine how changes in connectivity translate into changes in information flow and behavior using whole brain calcium imaging and behavioral experiments. In sum, our research program aims to establish the mechanisms, by which the environment changes synaptic hardwiring and behavior in the context of an asymmetric synaptic connection.

PI：你好，汉内斯·E。