Thalamostriatal circuit contributions to behavioral inflexibility following adolescent ethanol exposure
青少年乙醇暴露后丘脑纹状体回路对行为僵化的影响
基本信息
- 批准号:10579844
- 负责人:
- 金额:$ 21.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-03-01 至 2023-07-31
- 项目状态:已结题
- 来源:
- 关键词:AdolescentAdultAffectAlcohol consumptionAlcoholsAnatomyAnimalsAttentionBehaviorBehavioralBrainBrain regionCalciumCell NucleusCellsChronic DiseaseCognitiveCorpus striatum structureDorsalEconomic BurdenElectrophysiology (science)Exposure toFemaleFiberGeneticGlutamatesGoalsHeavy DrinkingImpairmentInterventionKnowledgeLearningLesionLifeMacaca mulattaMale AdolescentsMeasurementMeasuresMonitorMusNeurobiologyNeuronsOpsinOutcomePersonsPharmaceutical PreparationsPhotometryPhysiologyPsychological reinforcementPublic HealthRattusRecording of previous eventsReversal LearningRiskRodentRoleSliceSubstance Use DisorderSynapsesSynaptic TransmissionTestingThalamic NucleiThalamic structureWorkadolescent alcohol effectadolescent alcohol exposurealcohol and other drugalcohol behavioralcohol effectalcohol exposurealcohol misusealcohol use disorderassociated symptombehavior measurementbehavior testbehavioral impairmentbehavioral outcomebrain circuitrycalcium indicatorcognitive testingdrug misuseearly onsetemerging adultexperimental studyflexibilityfunctional adaptationhealth economicshigh riskhuman imagingimaging studyimprovedin vivoinsightmaladaptive behaviormaleneuroadaptationnonhuman primatenoveloptogeneticspatch clampresponsesocioeconomicsunderage drinking
项目摘要
Project Summary
Alcohol use disorder (AUD) is a chronic disease with substantial health and socioeconomic consequences.
Drinking alcohol during adolescence increases the risk of developing symptoms associated with AUD during
adulthood, including heavy drinking. The overarching goal of this project is to identify functional adaptations in
brain circuitry that are caused by adolescent alcohol exposure, and to determine the role of those adaptations
in maladaptive behaviors. Deficits in behavioral flexibility (i.e., impaired ability to alter behavior in response to
changes in the outcome of that behavior) are associated with drug and alcohol misuse. Previous studies show
that alcohol exposure during adolescence decreases behavioral flexibility in adult rodents. This proposal will
explore the impact of adolescent alcohol exposure on brain circuitry involved in behavioral flexibility.
Specifically, the proposed studies will determine the effects of adolescent alcohol exposure on neurons in the
centrolateral nucleus of the thalamus (CL) that project to the dorsomedial striatum (DMS). Lesion or inhibition
of these neurons causes deficits in behavioral flexibility in commonly used tasks including reversal learning and
attentional set-shifting. These deficits are similar to those observed after adolescent alcohol exposure;
however, the impact of alcohol on these neurons, and the involvement of CL neurons in alcohol-induced
deficits in behavioral flexibility, have not been explored. The central hypothesis is that adolescent alcohol
exposure reduces activity in DMS-projecting CL neurons, and that reduced CL neuron activity contributes to
impaired behavioral flexibility in male and female mice. The experiments in Aim 1 will compare the physiology
of CL neurons from adult alcohol-naïve mice and mice that were exposed to vaporized alcohol during
adolescence. Brain slice electrophysiology experiments will measure the intrinsic excitability of DMS-projecting
CL neurons as well as their excitatory and inhibitory synaptic inputs. To extend these findings to intact brain
circuits, activity of DMS-projecting CL neurons from alcohol-naïve mice and mice with a history of adolescent
alcohol exposure will be measured during reversal learning. Calcium dynamics in these neurons will be
monitored via fiber photometry using the genetically-encoded calcium indicator jGCaMP7s. Experiments in Aim
2 will test the hypothesis that increasing activity of DMS-projecting CL neurons using optogenetic stimulation
will improve behavioral flexibility in mice exposed to alcohol during adolescence. Results of these experiments
will provide important information about how adolescent alcohol exposure affects thalamostriatal circuitry in the
developing brain and how alcohol-induced changes in thalamostriatal physiology relate to maladaptive
behaviors that contribute to alcohol misuse in adulthood. Discovery of novel circuitry that is impacted by
adolescent alcohol exposure will inform strategies for manipulating circuit activity to reduce alcohol misuse.
项目总结
项目成果
期刊论文数量(1)
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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Kari Johnson其他文献
Kari Johnson的其他文献
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{{ truncateString('Kari Johnson', 18)}}的其他基金
Thalamostriatal circuit contributions to behavioral inflexibility following adolescent ethanol exposure
青少年乙醇暴露后丘脑纹状体回路对行为僵化的影响
- 批准号:
10354795 - 财政年份:2022
- 资助金额:
$ 21.92万 - 项目类别:
Presynaptic modulation of corticostriatal transmission following chronic ethanol exposure
慢性乙醇暴露后皮质纹状体传递的突触前调节
- 批准号:
10020296 - 财政年份:2017
- 资助金额:
$ 21.92万 - 项目类别:
Presynaptic modulation of corticostriatal transmission following chronic ethanol exposure
慢性乙醇暴露后皮质纹状体传递的突触前调节
- 批准号:
10241461 - 财政年份:2017
- 资助金额:
$ 21.92万 - 项目类别:
Metabotropic glutamate receptor-mediated synaptic plasticity in the basal ganglia
基底神经节代谢型谷氨酸受体介导的突触可塑性
- 批准号:
8258278 - 财政年份:2010
- 资助金额:
$ 21.92万 - 项目类别:
Metabotropic glutamate receptor-mediated synaptic plasticity in the basal ganglia
基底神经节代谢型谷氨酸受体介导的突触可塑性
- 批准号:
8097569 - 财政年份:2010
- 资助金额:
$ 21.92万 - 项目类别:
Metabotropic glutamate receptor-mediated synaptic plasticity in the basal ganglia
基底神经节代谢型谷氨酸受体介导的突触可塑性
- 批准号:
7909971 - 财政年份:2010
- 资助金额:
$ 21.92万 - 项目类别:
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