Gestational ethanol effects on dorsal striatal function and associated behaviors
Gestational ethanol effects on dorsal striatal function and associated behaviors
批准号:
9042902
负责人:
Verginia Carmella Cuzon Carlson
金额:
$24.9万
依托单位国家:
美国
项目类别:
财政年份:
2014
资助国家:
美国
项目状态:
已结题
起止时间:
2014-04-15 至 2017-06-30
关键词:
2-arachidonylglycerolAdultAge-MonthsAlcohol consumptionAlcoholsBasal GangliaBehaviorBehavioralBiologicalCNR1 geneCellsCenters for Disease Control and Prevention (U.S.)Congenital AbnormalityControl AnimalCorpus striatum structureDataDecision MakingDefectDorsalElectrophysiology (science)EmbryoEndocannabinoidsEnzyme InhibitionEnzymesEthanolExposure toFetal Alcohol Spectrum DisorderFetal Alcohol SyndromeGlutamatesHumanHuman DevelopmentHyperactive behaviorImpairmentImpulsivityIndividualInfantInterneuronsLateralLeadLearningManuscriptsMemory impairmentMentorsMolecularMovementMusNeuronsOperant ConditioningOutputParvalbuminsPhasePlayPregnancyProductionPsyche structureReportingResearchRoleSomatostatinSpecificitySymptomsSynapsesSystemTechnologyTestingViralWestern BlottingWomanalcohol effectanandamidebinge drinkingcannabinoidergic transmissionclassical conditioningdisabilitydrinkingendocannabinoid signalinghabit learninginhibitor/antagonistlearning strategylipoprotein lipasemotor deficitmotor disordermouse modelneural circuitneurotransmissionoptogeneticspartial recoverypatch clamppostnatalreceptorresearch studytransmission processvapor
中文摘要
拟议的研究计划的目的是调查妊娠乙醇(EtOH)的影响,
暴露于背侧纹状体回路,导致一些行为异常,如受损
在胎儿酒精谱系障碍中观察到的决策、冲动性增加和运动缺陷
(FASD)。使用小鼠模型,我们将通过蒸汽室将个体暴露于乙醇中,
胚胎期和出生后早期,以模仿人类发育的三个月
(妊娠期EtOH),并检查背侧纹状体回路的分布和相关行为,
成年迄今为止的初步研究结果表明,在暴露于妊娠期乙醇的成年小鼠中,
显示背侧纹状体(DLS)中GABA能传递减少,似乎涉及
增强内源性大麻素的调节作用。我们没有观察到妊娠期EtOH诱导的
电磁波传输。乙醇也会损害习惯学习,这是一种联想性的工具。
涉及DLS的调节。1将确定这些妊娠EtOH的机制
通过实现以下特定目标来实现效果:1)确定异常突触的突触特异性。
暴露于妊娠EtOH的小鼠DLS中的GABA能微电路。为了实现这一点,我提议病毒,
光遗传学和电生理学实验来检查三个主要的GABA能突触,
纹状体中棘神经元(MSNs),由小白蛋白中间神经元形成的那些,由其他神经元形成的那些,
MSN,和那些形成低阈值尖峰生长抑素中间神经元。2)妊娠期EtOH抢救
暴露于联想学习和纹状体神经传递:可能的治疗途径。使用
具体目标1,1中获得的信息将使用药理学试剂降低内源性大麻素浓度,
拯救受损的习惯学习和GABA能神经传递。综合考虑,
该项目将为评估纹状体GABA能微电路的中断
是FASD中许多行为异常的基础,并提出了补偿FASD的方法。
这些影响。
英文摘要
The objective of the proposed research plan is to investigate the effects of gestational ethanol (EtOH)
exposure on dorsal striatal circuitry that contribute to some of the behavioral abnormalities, such as impaired
decision making, increased impulsivity, and motor deficits that observed in Fetal Alcohol Spectrum Disorder
(FASD). Using a mouse model, we will expose individuals via a vapor chamber to ethanol throughout the
embryonic and early postnatal period in order to mimic the three trimesters of human development
(gestational EtOH) and examine the disposition of dorsal striatal circuitry and associated behaviors during
adulthood. Preliminary findings to date indicate that in adult mice that were exposed to gestational EtOH
display decreased GABAergic transmission in the dorsal lateral striatum (DLS) that appears to involve
increased modulation by endocannabinoids. We observed no gestational EtOH-induced effect of
glutamatergic transmission. Gestational EtOH also impairs habit learning; a type of associative instrumental
conditioning that involves the DLS. 1 will determine the mechanisms underlying these gestational EtOH
effects by accomplishing the following specific aims: 1) Determine the synaptic specificity of aberrant
GABAergic microcircuits in the DLS of mice exposed to gestational EtOH. To accomplish this 1 propose viral,
optogenetic, and electrophysiological experiments to examine the three major GABAergic synapses onto
striatal medium spiny neurons (MSNs), those formed by parvalbumin interneurons, those formed by other
MSNs, and those formed by low-threshold spiking somatostatin interneurons. 2) Rescue of gestational EtOH
exposure on associative learning and striatal neurotransmission: possible avenues for treatment. Using the
information gained in specific aim 1,1 will use pharmacological agents to decrease endocannabinoid tone to
rescue the impaired habit learning and GABAergic neurotransmission.Taken together, the completion of this
project will lay the groundwork for assessing how disruptions of the GABAergic microcircuitry of the striatum
underlie many of the behavioral abnormalities seen in FASD and suggest approaches to compensate for
these effects.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Project 7/8: INIA Stress and Chronic Alcohol Interactions: Cross-species studies of metabolic allostasis and altered striatal circuitry
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批准号:10590709
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项目类别:
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资助金额:$48.63万
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财政年份:2022
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负责人:Verginia Carmella Cuzon Carlson
-
依托单位:
Project 7/8: INIA Stress and Chronic Alcohol Interactions: Cross-species studies of metabolic allostasis and altered striatal circuitry
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批准号:10409985
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项目类别:
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资助金额:$48.48万
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财政年份:2022
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负责人:Verginia Carmella Cuzon Carlson
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依托单位:
Functional consequences of fetal-alcohol-induced brain growth abnormalities identified with in utero MRI
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批准号:10398204
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项目类别:
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资助金额:$68.88万
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财政年份:2021
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负责人:Verginia Carmella Cuzon Carlson
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依托单位:
Functional consequences of fetal-alcohol-induced brain growth abnormalities identified with in utero MRI
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批准号:10590615
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项目类别:
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资助金额:$67.35万
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财政年份:2021
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负责人:Verginia Carmella Cuzon Carlson
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依托单位:
Gestational ethanol effects on dorsal striatal function and associated behaviors
-
批准号:8810270
-
项目类别:
-
资助金额:$24.9万
-
财政年份:2014
-
负责人:Verginia Carmella Cuzon Carlson
-
依托单位:
Gestational ethanol effects on dorsal striatal function and associated behaviors
-
批准号:8838018
-
项目类别:
-
资助金额:$24.15万
-
财政年份:2014
-
负责人:Verginia Carmella Cuzon Carlson
-
依托单位:
In utero ethanol exposure & development of GABAergic cortical interneurons
-
批准号:7321656
-
项目类别:
-
资助金额:$4.2万
-
财政年份:2006
-
负责人:Verginia Carmella Cuzon Carlson
-
依托单位:
In utero ethanol exposure & development of GABAergic cortical interneurons
-
批准号:7222441
-
项目类别:
-
资助金额:$4.2万
-
财政年份:2006
-
负责人:Verginia Carmella Cuzon Carlson
-
依托单位:
7/8: INIA Stress and Chronic Alcohol Interactions: Stress and Ethanol Self Administration in Monkeys
-
批准号:10090536
-
项目类别:
-
资助金额:$45.07万
-
财政年份:2002
-
负责人:Verginia Carmella Cuzon Carlson
-
依托单位:
Translational examination of alcohol-associated epigenetic signatures: from primates to rodents
-
批准号:10056068
-
项目类别:
-
资助金额:$23.52万
-
财政年份:1996
-
负责人:Verginia Carmella Cuzon Carlson
-
依托单位:
Translational examination of alcohol-associated epigenetic signatures: from primates to rodents
-
批准号:10544312
-
项目类别:
-
资助金额:$15.3万
-
财政年份:1996
-
负责人:Verginia Carmella Cuzon Carlson
-
依托单位:
Translational examination of alcohol-associated epigenetic signatures: from primates to rodents
-
批准号:10350582
-
项目类别:
-
资助金额:$21.87万
-
财政年份:1996
-
负责人:Verginia Carmella Cuzon Carlson
-
依托单位:
海外基金