Dissecting hypothalamic pathways that regulate sexually dimorphic behaviors
剖析调节性二态性行为的下丘脑通路
基本信息
- 批准号:9351259
- 负责人:
- 金额:$ 35.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-05-15 至 2020-04-30
- 项目状态:已结题
- 来源:
- 关键词:AblationAcuteAdultAffectAggressive behaviorAnxietyApoptoticApplications GrantsAreaBehaviorBehavior ControlBehavioralBehavioral AssayBiological AssayBrainCell NucleusCellsCholera ToxinClinicalClozapineCognitionDevelopmentDiagnosticFOS geneFemaleFunctional disorderGenesGeneticGenetic studyGoalsHealthHypothalamic structureInternal Ribosome Entry SiteKnock-in MouseLabelLigandsLinkLocalized LesionMapsMental disordersMetabolicModelingMolecularMolecular GeneticsMotorMouse StrainsMusNerve DegenerationNeurodegenerative DisordersNeuroepithelial, Perineurial, and Schwann Cell NeoplasmNeurogliaNeuronsNeurosecretory SystemsOxidesPartner in relationshipPathway interactionsPharmacology StudyPhysiologicalProgesterone ReceptorsProsencephalonReagentRegulationResearch Project GrantsRetrievalRoleSex CharacteristicsSocial BehaviorSocial ControlsStructureTerritorialityTestingTherapeuticTracerViralVirusWorkanthrax lethal factorbehavior testcell typecognitive functiondesigner receptors exclusively activated by designer drugsemotional behaviorexperimental studyfeedinggenetic approachin vivoinnovationinsightmalematernal aggressionmotor controlmouse Cre recombinasenervous system disorderneural circuitnovelnovel diagnosticsnovel therapeutic interventionprogesterone receptor Apublic health relevancepupreceptorrelating to nervous systemsextumor
项目摘要
DESCRIPTION (provided by applicant): This grant application seeks to define the genetic and neural circuit basis of the functional role of the ventromedial hypothalamus (VMH). The VMH is molecularly heterogeneous and correspondingly, it has been implicated in the regulation of diverse behaviors and physiological function: motor and visceromotor functions, neuroendocrine function, feeding, and sexually dimorphic social and emotional behaviors. One appealing possibility is that these diverse functions are controlled by discrete subsets of VMH neurons. We and others have identified a small cluster of sexually dimorphic neurons within the VMH. We hypothesize that these neurons control sexually dimorphic social and emotional behaviors. In Aim 1, we will use a novel Cre recombinase mouse strain we have generated to genetically trace the connections of these dimorphic VMH neurons. We will also test the hypothesis that projections to different areas emanating from these dimorphic neurons are activated during distinct behaviors. In Aim 2, we will utilize a novel Cre-dependent, pro-apoptotic gene to genetically ablate these dimorphic VMH neurons in adult males and females. These mice will subsequently be tested for deficits in dimorphic social and emotional behaviors. In Aim 3, we will utilize a Cre- dependent heterologous receptor (DREADD) activated by a heterologous ligand (clozapine-N-oxide) to switch on activity in these VMH neurons in vivo in males and females. This experiment will test whether activity in these neurons is sufficient to elicit dimorphic socia and emotional behavior. Taken together, our molecular genetic approaches will uncover the connectivity and functional relevance of a sexually dimorphic neuronal cluster in the mammalian forebrain. Health Relatedness: The devastating clinical manifestations of common neurodegenerative conditions and psychiatric conditions often reflect dysfunction of specific neural circuits. The VMH has been implicated in the regulation of social and emotional behaviors, neuroendocrine function, feeding, and motor and visceromotor function. VMH-localized lesions such as tumors result in altered cognition, abnormal social behaviors, and metabolic changes. Our studies will provide novel mechanistic insight into the functional relevance of the VMH and the circuits in which it participates in health. These findings may ultimately allow development of more rationally-targeted diagnostic and therapeutic options for VMH dysfunction in neurological disorders. Finally, the Cre-dependent, pro-apoptotic genetically encoded reagent that we use in this proposal will be useful in developing models of "neurodegeneration" in any neuronal (or other cell) type.
DESCRIPTION (provided by applicant): This grant application seeks to define the genetic and neural circuit basis of the functional role of the ventromedial hypothalamus (VMH). The VMH is molecularly heterogeneous and correspondingly, it has been implicated in the regulation of diverse behaviors and physiological function: motor and visceromotor functions, neuroendocrine function, feeding, and sexually dimorphic social and emotional behaviors. One appealing possibility is that these diverse functions are controlled by discrete subsets of VMH neurons. We and others have identified a small cluster of sexually dimorphic neurons within the VMH. We hypothesize that these neurons control sexually dimorphic social and emotional behaviors. In Aim 1, we will use a novel Cre recombinase mouse strain we have generated to genetically trace the connections of these dimorphic VMH neurons. We will also test the hypothesis that projections to different areas emanating from these dimorphic neurons are activated during distinct behaviors. In Aim 2, we will utilize a novel Cre-dependent, pro-apoptotic gene to genetically ablate these dimorphic VMH neurons in adult males and females. These mice will subsequently be tested for deficits in dimorphic social and emotional behaviors. In Aim 3, we will utilize a Cre- dependent heterologous receptor (DREADD) activated by a heterologous ligand (clozapine-N-oxide) to switch on activity in these VMH neurons in vivo in males and females. This experiment will test whether activity in these neurons is sufficient to elicit dimorphic socia and emotional behavior. Taken together, our molecular genetic approaches will uncover the connectivity and functional relevance of a sexually dimorphic neuronal cluster in the mammalian forebrain. Health Relatedness: The devastating clinical manifestations of common neurodegenerative conditions and psychiatric conditions often reflect dysfunction of specific neural circuits. The VMH has been implicated in the regulation of social and emotional behaviors, neuroendocrine function, feeding, and motor and visceromotor function. VMH-localized lesions such as tumors result in altered cognition, abnormal social behaviors, and metabolic changes. Our studies will provide novel mechanistic insight into the functional relevance of the VMH and the circuits in which it participates in health. These findings may ultimately allow development of more rationally-targeted diagnostic and therapeutic options for VMH dysfunction in neurological disorders. Finally, the Cre-dependent, pro-apoptotic genetically encoded reagent that we use in this proposal will be useful in developing models of "neurodegeneration" in any neuronal (or other cell) type.
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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Nirao Mahesh Shah其他文献
Nirao Mahesh Shah的其他文献
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{{ truncateString('Nirao Mahesh Shah', 18)}}的其他基金
Genomic and neural circuit characterization of interoceptive experience-modulated female behavior in mice
小鼠内感受体验调节雌性行为的基因组和神经回路特征
- 批准号:
10586990 - 财政年份:2022
- 资助金额:
$ 35.41万 - 项目类别:
Genomic and neural circuit characterization of interoceptive experience-modulated female behavior in mice
小鼠内感受体验调节雌性行为的基因组和神经回路特征
- 批准号:
10762996 - 财政年份:2022
- 资助金额:
$ 35.41万 - 项目类别:
Functional dissection of a molecularly identified female-specific neural pathway in mice
分子鉴定的小鼠雌性特异性神经通路的功能解剖
- 批准号:
10503353 - 财政年份:2022
- 资助金额:
$ 35.41万 - 项目类别:
Characterization of Sexual Dimorphism in the Brain
大脑性别二态性的表征
- 批准号:
10166218 - 财政年份:2020
- 资助金额:
$ 35.41万 - 项目类别:
Dissecting hypothalamic pathways that regulate sexually dimorphic behaviors
剖析调节性二态性行为的下丘脑通路
- 批准号:
8562357 - 财政年份:2013
- 资助金额:
$ 35.41万 - 项目类别:
Dissecting hypothalamic pathways that regulate sexually dimorphic behaviors
剖析调节性二态性行为的下丘脑通路
- 批准号:
8661799 - 财政年份:2013
- 资助金额:
$ 35.41万 - 项目类别:
Dissecting hypothalamic pathways that regulate sexually dimorphic behaviors
剖析调节性二态性行为的下丘脑通路
- 批准号:
8990696 - 财政年份:2013
- 资助金额:
$ 35.41万 - 项目类别:
Dissecting hypothalamic pathways that regulate sexually dimorphic behaviors
剖析调节性二态性行为的下丘脑通路
- 批准号:
9057153 - 财政年份:2013
- 资助金额:
$ 35.41万 - 项目类别:
Dissecting the neural control of social attachment
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8536385 - 财政年份:2009
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$ 35.41万 - 项目类别:
Dissecting the neural control of social attachment
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- 批准号:
8296585 - 财政年份:2009
- 资助金额:
$ 35.41万 - 项目类别:
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