Prefrontal Circuit Control of Isolation-Induced Aggression
孤立诱发攻击的前额叶回路控制
基本信息
- 批准号:10638671
- 负责人:
- 金额:$ 67.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-03-06 至 2028-01-31
- 项目状态:未结题
- 来源:
- 关键词:Aggressive behaviorBehaviorBiological AssayBrainBrain regionCOVID-19 pandemicCellsCognitive TherapyColorCoupledDataDevelopmentDomestic ViolenceEndoscopyEpidemicHouse miceHousingHypothalamic structureImageInterneuronsLeadLonelinessMachine LearningMedialMediatingMediatorMental disordersModernizationMolecular GeneticsMusNeurokinin BNeuromedin K ReceptorNeuronsNeuropeptidesObesityPathologicPerceptionPopulationPrefrontal CortexPublic HealthResearchRisk FactorsRoleSignal TransductionSmokingSocial ControlsSocial isolationSocializationSocietiesSystemTachykininTechnologyTestingTextilesTherapeutic InterventionViolenceaging populationattenuationbehavior testcognitive controlgain of functiongamma-Aminobutyric Acidgene functionhippocampal pyramidal neuronin vivoloss of functionneuralneural patterningopioid epidemicoptogeneticspoor health outcomeschool shootingsocialsocial contactsocial deprivationsocial groupsocial mediasocial structuresuicide rate
项目摘要
PROJECT SUMMARY/ ABSTRACT
Extended deprivation of social contact can produce deleterious effects on the brain and behavior. Social isolation
(SI), or its perception (loneliness), is as predictive a risk factor for poor health outcomes as smoking or obesity.
Many factors have contributed to a modern epidemic of loneliness: a growing aging population, dramatic changes
to our social structure (technology, social media), the opioid crisis, and, most recently, the COVID-19 pandemic.
One of the most damaging impacts of SI is the promotion of interpersonal aggression and violence against others
– indeed, SI-associated domestic violence has risen by 20%, rates of suicide have surged, and school shootings
continue to rip at the fabric of society. Despite this, we have a poor understanding of the genetically-defined,
circuit mechanisms that give rise to isolation-induced aggression, representing a critical barrier for the
development of targeted interventions and cognitive therapies to treat pathological forms of aggression. One key
brain region known to exert top-down, cognitive control over behavior, including aggression, is the medial
prefrontal cortex (mPFC). However, the role of the mPFC in modulating the effects of SI-induced aggression is
unknown. In the project proposed here, we will interrogate the function of distinct, genetically-defined cells in the
mPFC to modulate SI-induced aggression. In support of this, we recently identified the neuropeptide Tachykinin
2 (Tac2)/Neurokinin B (NkB) as a key, subcortical mediator of SI. Here, we will test whether Tac2 signaling in
the mPFC exerts cortical control of SI-aggression. In preliminary studies, we have discovered that Tac2+ mPFC
neurons comprise a unique, unexplored class of GABAergic interneurons (INs). These findings lead to the
specific hypothesis that Tac2+ INs exert feed-forward inhibition of excitatory pyramidal neurons (PNs) to mediate
SI-aggression. To test this, we will combine behavior, machine learning, molecular-genetic loss- and gain-of
function manipulations, and in vivo Ca2+ imaging to achieve a circuit-level, mechanistic understanding of how
distinct populations of genetically-defined neurons in the mPFC exert coordinated, cortical control of SI-
aggression. We will determine whether mPFC Tac2+ neurons are required for SI-aggression (Aim 1), whether
mPFC PNs are sufficient to inhibit SI-aggression (Aim 2), and whether Tac2+ INs directly regulate PN activity
during SI-aggression (Aim 3). Collectively, we aim to uncover a conserved, genetically-defined mPFC
microcircuit for the top-down, cortical control of isolation-induced aggression. These findings will transform the
field by expanding our understanding of how pathological forms of aggression are encoded and controlled by
prefrontal circuits in the brain. Importantly, this research will have profound implications for the treatment of social
isolation-related mental health disorders, particularly those that result in violence.
项目摘要/摘要
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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Moriel Zelikowsky其他文献
Moriel Zelikowsky的其他文献
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{{ truncateString('Moriel Zelikowsky', 18)}}的其他基金
Genetic dissection of neural circuits underlying trauma, fear, and social behavior
对创伤、恐惧和社会行为背后的神经回路进行基因剖析
- 批准号:
9978917 - 财政年份:2019
- 资助金额:
$ 67.24万 - 项目类别:
Genetic dissection of neural circuits underlying trauma, fear, and social behavior
对创伤、恐惧和社会行为背后的神经回路进行基因剖析
- 批准号:
9927083 - 财政年份:2019
- 资助金额:
$ 67.24万 - 项目类别:
Genetic dissection of neural circuits underlying trauma, fear, and social behavior
对创伤、恐惧和社会行为背后的神经回路进行基因剖析
- 批准号:
9319813 - 财政年份:2016
- 资助金额:
$ 67.24万 - 项目类别:
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