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Ethanol and brain state-dependent neural signaling

乙醇和大脑状态依赖性神经信号传导

基本信息

批准号：
10190737
负责人：
Martin Paukert
金额：
$ 33.98万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
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：
2017-09-05 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10190737
关键词：
Acute Adrenergic Receptor Affect Alcohol consumption Alcohols Alzheimer&apos s Disease Astrocytes Ataxia Attention Behavior Behavioral Behavioral Paradigm Brain Brain region Cerebellum Complement Data Dose Drunk driving Electrophysiology (science)Ethanol Exercise Fiber Foundations GIRK2 subunit, G protein-coupled inwardly-rectifying potassium channel GLAST Protein Goals Head Image Impairment Individual Inositol Investigation Knock-out Knockout Mice Link Locomotion Memory Modeling Molecular Mouse Cell Line Mus Nerve Degeneration Neuraxis Neuroglia Neurologic Neurons Norepinephrine Parkinson Disease Pharmacology Phase Physiology Play Process Protocols documentation Purkinje Cells Rest Role Signal Transduction Slice Structure Structure of molecular layer of cerebellar cortex Structure of purkinje fibers Supporting Cell Synapses Synaptic plasticity System Testing Traffic accidents Transgenic Mice Work alcohol effect alcohol exposure alcohol sensitivity area striata autism spectrum disorder awake brain cell cell type cost experimental study genetic manipulation granule cell in vivo locus ceruleus structure motor impairment neurobehavioral neuroregulation neurotransmission noradrenergic novel receptor response selective expression sensor treadmill two photon microscopy two-photon

项目摘要

Alcohol consumption impairs motor coordination, attentional efforts and memory function. Alcohol-impaired driving accounted in 2013 for ~31% of all traffic accidents resulting in 10,076 fatalities and $59 billion crash-related cost. We propose to study the mechanisms how ethanol affects brain state-dependent neural signaling. Brain state-dependent signaling comprises adjustments in cellular and circuit activity to optimize how the brain processes information in a distinct behavioral context. We and others have used a locomotion paradigm to reveal that noradrenergic signaling is involved when such optimizations occur. At transitions from rest to locomotion astroglia, the support cells in the central nervous system, are norepinephrine-dependently activated simultaneously in brain regions as disparate as the cerebellum and primary visual cortex. The noradrenergic system is involved to support attentional efforts and in gating synaptic plasticity. It has long been known that alcohol can suppress the activity of locus coeruleus, the structure where noradrenergic neurons are clustered; however, it is still unclear what the consequences are for the activity of individual brain cells during active behavior. We propose to test the hypothesis that alcohol severely impairs brain state-dependent noradrenergic neuromodulation in an astroglia-dependent manner. Our approach is to combine specific mouse lines for cell type-selective genetic manipulation and expression of Ca2+ sensors with our motorized linear treadmill and two-photon microscopy to study Ca2+ dynamics and electrical activity in well-controlled behavioral states. These in vivo investigations will be complemented with acute slice Ca2+ imaging and electrophysiology experiments. We will focus our investigations on the cerebellum for its relatively straightforward circuit arrangement that facilitates mechanistic studies. The novel utilization of a specific Cre mouse line will enable us to selectively manipulate Bergmann glia, the astrocytes of the cerebellar molecular layer, but not astrocytes of the granule cell layer. We will pursue the following aims: (1) We will define extent and mechanism of the effect of acute ethanol on locomotion-induced Bergmann glia Ca2+ activation. (2) We will reveal ethanol-sensitive components of locomotion-induced Purkinje cell Ca2+ dynamics and dissect the relationship to Bergmann glia function. (3) We will investigate how locomotion- induced Purkinje cell Ca2+ dynamics regulate intrinsic and synaptic activity. Upon conclusion of our proposed studies we will have learned what components of brain state-dependent noradrenergic neural signaling are impaired by ethanol. This work will reveal how ethanol might exert its detrimental effects on attentional efforts and memory on the cellular and circuit level. These studies will further build the groundwork for future research on brain state-dependent neural signaling under neurodegenerative and neurobehavioral conditions associated with changes in noradrenergic signaling, such as Alzheimer's disease, Parkinson's disease and autism spectrum disorder.

饮酒会损害运动协调、注意力和记忆功能。Alcohol-impaired

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Noradrenergic terminal short-term potentiation enables modality-selective integration of sensory input and vigilance state.

DOI：
10.1126/sciadv.abk1378
发表时间：
2021-12-17
期刊：
Science advances
影响因子：
13.6
作者：
Gray SR;Ye L;Ye JY;Paukert M
通讯作者：
Paukert M

Constraints of vigilance-dependent noradrenergic signaling to mouse cerebellar Bergmann glia.

警惕依赖性去甲肾上腺素能信号对小鼠小脑伯格曼神经胶质细胞的限制。

DOI：
10.1002/glia.24350
发表时间：
2023
期刊：
Glia
影响因子：
6.2
作者：
Salinas-Birt,Angelica;Zhu,Xiangyu;Lim,EuniceY;CruzSantory,AryanaJ;Ye,Liang;Paukert,Martin
通讯作者：
Paukert,Martin

Comparison of GCaMP3 and GCaMP6f for studying astrocyte Ca2+ dynamics in the awake mouse brain.