THE ROLE OF MEDIUM SPINY NEURONS IN SLEEP DEPRIVATION-INDUCED COGNITIVE RIGIDITY.
THE ROLE OF MEDIUM SPINY NEURONS IN SLEEP DEPRIVATION-INDUCED COGNITIVE RIGIDITY.
批准号:
10656057
负责人:
Christopher John Davis
金额:
$22.95万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-03-01 至 2025-02-28
关键词:
AccelerationAccidentsAdenosineAffectAnimalsAreaBehaviorBehavioralBindingBiochemicalBrainCause of DeathCell membraneCellsCognitiveComplexCorpus striatum structureCyclic AMPDataDecelerationDecision MakingDopamineDopamine D2 ReceptorDorsalElectrophysiology (science)EventFeedbackFutureGABA ReceptorGeneticGoalsHumanImageLeadLiteratureMeasuresMediatingMediatorModelingMusNeuronsOccupationsOutcomeOutputPathway interactionsPerformancePopulationPredispositionPrimatesPublishingPurinergic P1 ReceptorsRattusRecoveryResistanceRisk FactorsRodentRoleSignal TransductionSleepSleep DeprivationSleep Wake CycleSolidStructureTechniquesTestingTimeTransgenic MiceWhole OrganismWorkawakecell typecognitive functioncognitive performancecognitive processcognitive rigidityexperimental studyflexibilityin vivoneuronal excitabilitypoor sleeppressurepreventreceptorreceptor densityreceptor expressionresponsestemtouchscreen
中文摘要
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英文摘要
ABSTRACT
This project is focused on understanding the mechanisms behind performance deficits that occur with
insufficient sleep. In particular, studies in humans have identified cognitive rigidity (compromised situational
adaptability in decision making) as a consequence of sleep deprivation (SD). Cognitive rigidity is influenced by
a striatopallidal brain circuit that is conserved in subhuman primates and rodents and involves a cell type that
expresses dopamine-type 2 (DrD2) and adenosine-type 2a (A2a) receptors. In the current studies, we will
employ mouse electrophysiology recordings and real-time striatal event imaging, in addition to a rat cognitive
flexibility task that is susceptible to SD. We will apply these techniques to transgenic mouse and rat models in
order to interrogate the role of the DrD2/A2a striatopallidal brain circuit in mediating the effects of SD at the
biochemical, receptor, regional (brain structure and electrophysiology) levels in addition to probing complex
whole organism behavior. In Aim 1, we will determine the extent to which DrD2 cell membrane localization and
intracellular cyclic adenosine monophosphate concentration ([cAMP]i) in striatal medium spiny neurons vary as
a function of spontaneous and SD-induced sleep/wake cycles. This experiment will address our dynamic
interplay hypothesis that striatal DrD2 receptor availability and the inversely-related [cAMP]i function as cellular
mediators of sleep pressure in the striatum. In Aim 2, we will examine whether the activity of striatal DrD2/A2a
cells is necessary and sufficient to confer the negative impacts of SD on cognitive flexibility. We predict that
cell-type specific chemogenetic activation or inactivation of these neurons will mimic or rescue, respectively,
the behavioral consequences of SD in a touchscreen operant reversal task. The anticipated results of this
project will confirm the mechanistic role of the striatopallidal medium spiny neuron population in the
performance decrements that stem from sleep loss. Here, our focus is on dopaminergic signaling, but our
long-term objective is to elucidate how signaling mechanisms in the striatum and connected brain areas
converge to regulate the cognitive processes that are compromised by SD. Overall, this work will set the stage
for future inquiries by confirming cell type-specific SD mitigation targets in striatal circuitry. It will also inform
the public and scientific constituencies of potential mechanistic and compensatory approaches to
reversing/preventing the deleterious effects of sleep loss.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
"Uncoupling sleep deprivation-associated stressors from sleep loss in rodents"
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批准号:8822760
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项目类别:
-
资助金额:$22.0万
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财政年份:2014
-
负责人:Christopher John Davis
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依托单位:
海外基金