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Noradrenergic gating of astrocyte calcium-mediated homeostasis in vivo

星形胶质细胞钙介导体内稳态的去甲肾上腺素能门控

基本信息

批准号：
10679269
负责人：
Cameron Lewis Smith
金额：
$ 4.77万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10679269
关键词：
Adrenergic Receptor Affect Animals Area Arousal Astrocytes Attention Behavior Behavioral Brain Ca(2+)-Transporting ATPase Calcium Calcium Oscillations Calcium Signaling Data Ensure Event Exhibits Generations Glutamates Goals Heterogeneity Homeostasis Human Impairment Linear Models Link Literature Locomotion Machine Learning Mammals Measurement Measures Mediating Methods Microscope Modeling Mus Mydriasis Neuromodulator Neuromodulator Receptors Neurons Neurophysiology - biologic function Norepinephrine Norepinephrine Receptors Performance Personal Satisfaction Play Population Positioning Attribute Primates Process Pupil Regulation Reporter Rodent Role Running Sensory Shapes Signal Pathway Signal Transduction Site Stimulus Techniques Testing Time Visual Cortex Wakefulness Work alertness awake experimental study high dimensionality in vivo multiphoton imaging neural neuroregulation neurotransmission noradrenergic novel optogenetics response sensor tool

项目摘要

PROJECT SUMMARY Humans and mice show various brain states which are integral for survival and well-being. In awake mice, alert brain states are distinguished by locomotion, whisking, or pupil dilation in the absence of overt behavior. These accompany changes in neural function within the cortex such as reduced population correlation, increased sensory response, and reduced oscillatory activity. In addition, norepinephrine (NE) levels are increased in cortex during these activated periods. These findings are consistent with a long literature linking NE to alertness, attention, and behavioral performance in primates and rodents. Our project is focused on understanding changes in cortical astrocyte activity during these aroused brain states. Astrocyte calcium activity increases during both running and pupil dilation, but the heterogeneity of this response and the relative contribution of neuromodulators or local changes in neural activity to these astrocytic calcium events is not well understood. Conversely, astrocyte calcium events may be important for regulating processes such as glutamate homeostasis that directly impact neural activity on short timescales, but these effects have not been well-characterized in vivo. Thus, the overall goal of this project is to understand the local and global factors contributing to changes in astrocyte calcium activity and the effect of astrocyte calcium on local networks of neurons. We hypothesize that noradrenergic neuromodulation drives calcium-mediated increases in glutamate homeostasis that facilitate and/or support changes in local neuronal brain state. To test this hypothesis, we will first investigate the heterogeneity of somatic and microdomain calcium waves in response to NE increases during alert brain states. We will then test the effects of artificially reducing astrocyte calcium on state changes in local populations of neurons, and whether reducing astrocyte calcium responses to NE locally affects glutamate homeostasis. Our final experiment will use optogenetics to test the sufficiency of NE signaling pathways for any observed changes and the necessity of astrocyte calcium for these induced changes. The results of this project will more clearly define the upstream and downstream mechanisms of calcium signaling within astrocytes across different brain states and their effect on neural populations.

项目总结