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
- 批准号:10397093
- 负责人:
- 金额:$ 17.37万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-05-01 至 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAffectAlcohol consumptionAlcohol dependenceAlcoholsAnimalsBathingBehaviorBehavior ControlBehavioralBiophysicsBrainBrain regionCell physiologyCellsCommunicationComplexConsumptionDataElectrophysiology (science)Exposure toFoundationsFutureGlutamatesGoalsHippocampus (Brain)ImpairmentInterneuronsIntoxicationIntuitionLeadMeasuresMedialMicrodialysisModelingMolecularNeuronsNeurophysiology - biologic functionNeurosciencesOralOutcomePatternPharmacodynamicsPharmacologic ActionsPharmacologyPhysiologicalPlayPrefrontal CortexPreparationPropertyProtocols documentationPublishingRattusRecording of previous eventsRegulationReportingRisk BehaviorsRisk-TakingRodentRoleSeriesSliceSubstance Use DisorderSumSynapsesSystemTestingTransgenic OrganismsTranslatingViolenceWorkalcohol effectalcohol exposurealcohol use disorderawakebehavioral impairmentbiophysical propertiescell typecognitive functiondrinkingexperimental studyhippocampal pyramidal neuronhypnoticin vivoinnovationinsightinterdisciplinary approachmaladaptive behaviormotivational processesneural circuitneural modelnoveloptogeneticspatch clamprelating to nervous systemsedativetherapy development
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)
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CHRISTOPHER COURT LAPISH其他文献
CHRISTOPHER COURT LAPISH的其他文献
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{{ 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:
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