Determining the acute pharmacological effects of alcohol in rodent medial prefrontal cortex

确定酒精对啮齿动物内侧前额皮质的急性药理作用

基本信息

项目摘要

Project Summary: A wealth of data exists describing how alcohol influences neuronal function in brain regions necessary for complex cognitive functions such prefrontal cortex (PFC). These data have proven critical to form hypotheses regarding how alcohol consumption might lead to altered behavioral states (e.g. intoxication) and the associated negative outcomes (e.g. risky behavior, violence). However, these data have been exclusively collected in reduced preparations, such as anesthetized animals or ex vivo slice preparations, and therefore may not adequately model how neural function is impaired by alcohol consumption in behaving subjects. Published and preliminary data from our group indicate that the broad reductions in neural firing previously observed in reduced preparations are not observed in awake behaving animals. This calls into question current explanations of how alcohol affects neural function, indicating that there is a critical need for additional experiments that demonstrate specifically how alcohol consumption affects neural function in the PFC of awake behaving animals. The long-term goal of this work is to create a unified model of how alcohol consumption alters the computational properties of PFC and leads to impaired behavioral control. Towards this goal, a series of experiments are proposed in rat models to test the overarching hypothesis that alcohol consumption leads to reductions in functional connectivity in PFC networks. In Specific Aim 1, a series of in vivo approaches will determine how oral consumption of alcohol influences neural activity in medial PFC (mPFC) networks. A combination of microdialysis, large-scale neural recordings, and optogenetics will be performed to determine the cell type- and layer-specific effects of alcohol consumption on neural activity. Experiments will be performed to determine which changes in neural activity evoked by oral consumption are conserved following local application of physiologically-relevant concentrations of alcohol within mPFC. Specific Aim 2 will determine which changes in neural activity observed in vivo are conserved ex vivo. In this Aim we will trace the local effects of alcohol on mPFC from the single cell to the microcircuit level. Glutamate uncaging will be combined with patch-clamp electrophysiology to assess network function and single cell function. These approaches will synergize with those in Specific Aim 1 to determine which changes in neural activity following alcohol consumption are conserved across levels of neural function and in each preparation. Collectively, these data will facilitate future studies that will integrate how the influence of consumed alcohol on cellular function translates into altered network properties and, ultimately, impaired behavioral states. Future studies will also assess changes in neural function in brain-wide networks and if/how the observations herein are altered following extended alcohol use. In sum, this proposal seeks to clarify a long held misconception in the alcohol field and answer a fundamental question on how alcohol effects neural activity.
Project Summary: A wealth of data exists describing how alcohol influences neuronal function in brain regions necessary for complex cognitive functions such prefrontal cortex (PFC). These data have proven critical to form hypotheses regarding how alcohol consumption might lead to altered behavioral states (e.g. intoxication) and the associated negative outcomes (e.g. risky behavior, violence). However, these data have been exclusively collected in reduced preparations, such as anesthetized animals or ex vivo slice preparations, and therefore may not adequately model how neural function is impaired by alcohol consumption in behaving subjects. Published and preliminary data from our group indicate that the broad reductions in neural firing previously observed in reduced preparations are not observed in awake behaving animals. This calls into question current explanations of how alcohol affects neural function, indicating that there is a critical need for additional experiments that demonstrate specifically how alcohol consumption affects neural function in the PFC of awake behaving animals. The long-term goal of this work is to create a unified model of how alcohol consumption alters the computational properties of PFC and leads to impaired behavioral control. Towards this goal, a series of experiments are proposed in rat models to test the overarching hypothesis that alcohol consumption leads to reductions in functional connectivity in PFC networks. In Specific Aim 1, a series of in vivo approaches will determine how oral consumption of alcohol influences neural activity in medial PFC (mPFC) networks. A combination of microdialysis, large-scale neural recordings, and optogenetics will be performed to determine the cell type- and layer-specific effects of alcohol consumption on neural activity. Experiments will be performed to determine which changes in neural activity evoked by oral consumption are conserved following local application of physiologically-relevant concentrations of alcohol within mPFC. Specific Aim 2 will determine which changes in neural activity observed in vivo are conserved ex vivo. In this Aim we will trace the local effects of alcohol on mPFC from the single cell to the microcircuit level. Glutamate uncaging will be combined with patch-clamp electrophysiology to assess network function and single cell function. These approaches will synergize with those in Specific Aim 1 to determine which changes in neural activity following alcohol consumption are conserved across levels of neural function and in each preparation. Collectively, these data will facilitate future studies that will integrate how the influence of consumed alcohol on cellular function translates into altered network properties and, ultimately, impaired behavioral states. Future studies will also assess changes in neural function in brain-wide networks and if/how the observations herein are altered following extended alcohol use. In sum, this proposal seeks to clarify a long held misconception in the alcohol field and answer a fundamental question on how alcohol effects neural activity.

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

CHRISTOPHER COURT LAPISH其他文献

CHRISTOPHER COURT LAPISH的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('CHRISTOPHER COURT LAPISH', 18)}}的其他基金

CORE 1/2: INIA Stress and Chronic Alcohol Interactions: Computational and Statistical Analysis Core (CSAC)
CORE 1/2:INIA 压力和慢性酒精相互作用:计算和统计分析核心 (CSAC)
  • 批准号:
    10411629
  • 财政年份:
    2022
  • 资助金额:
    $ 17.37万
  • 项目类别:
CORE 1/2: INIA Stress and Chronic Alcohol Interactions: Computational and Statistical Analysis Core (CSAC)
CORE 1/2:INIA 压力和慢性酒精相互作用:计算和统计分析核心 (CSAC)
  • 批准号:
    10574618
  • 财政年份:
    2022
  • 资助金额:
    $ 17.37万
  • 项目类别:
Determining the acute pharmacological effects of alcohol in rodent medial prefrontal cortex
确定酒精对啮齿动物内侧前额皮质的急性药理作用
  • 批准号:
    10194666
  • 财政年份:
    2021
  • 资助金额:
    $ 17.37万
  • 项目类别:
Prefrontal cortex regulation of ethanol-reinforced behavior
前额皮质对乙醇强化行为的调节
  • 批准号:
    9240555
  • 财政年份:
    2015
  • 资助金额:
    $ 17.37万
  • 项目类别:
Network Analysis and Computational Modeling Core
网络分析和计算建模核心
  • 批准号:
    10526832
  • 财政年份:
    1989
  • 资助金额:
    $ 17.37万
  • 项目类别:
Corticostriatal processing of alcohol-paired cues in aversion-resistant drinking
厌恶性饮酒中酒精配对线索的皮质纹状体处理
  • 批准号:
    10310679
  • 财政年份:
    1989
  • 资助金额:
    $ 17.37万
  • 项目类别:

相似海外基金

How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 17.37万
  • 项目类别:
    Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 17.37万
  • 项目类别:
    Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 17.37万
  • 项目类别:
    Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 17.37万
  • 项目类别:
    Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 17.37万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 17.37万
  • 项目类别:
    Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 17.37万
  • 项目类别:
    Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 17.37万
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    $ 17.37万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    $ 17.37万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了