Intrinsic CRF signaling within the lateral habenula
外侧缰核内的内在 CRF 信号传导
基本信息
- 批准号:10667070
- 负责人:
- 金额:$ 22.78万
- 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:2023-03-02 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:Anti-Anxiety AgentsAnxietyApplications GrantsAtlasesAxonBehaviorBehavioralBrainBrain regionCRH geneCalciumCorticotropin-Releasing HormoneCorticotropin-Releasing Hormone ReceptorsCyclic AMP-Dependent Protein KinasesDarknessDataDrug AddictionElectrophysiology (science)ExhibitsFemaleFunctional disorderGABA ReceptorGeneticGlutamate ReceptorGlutamatesGoalsHabenulaHypothalamic structureImageImmunohistochemistryIn VitroInterneuronsKnowledgeLabelLateralLightLoxP-flanked alleleMediatingMediatorMental DepressionMental disordersMessenger RNAMotivationMusNegative ReinforcementsNeuronsNeuropeptidesNeurosecretory SystemsPhenotypePlayPopulationPositive ReinforcementsPredispositionProxyPsychopathologyPublishingRattusRegulationReporterResearchRoleSex BiasSignal TransductionSourceStressSynapsesSystemTestingViralanxiety-related behavioranxiety-related disordersbehavioral outcomebehavioral responsebrain reward regionsdepressive symptomsexperimental studygamma-Aminobutyric Acidgenetic approachhypothalamic-pituitary-adrenal axisinnovationmalemotivated behaviormouse geneticsneural circuitneurochemistryneuronal excitabilityneuroregulationneurotransmissionnoveloptogeneticspostsynapticpre-clinicalpresynapticreceptorrelease factorresponsereward processingsexsexual dimorphismsource localizationstress related disorderstressorvirus genetics
项目摘要
Abstract
Corticotropin releasing factor (CRF) released from the hypothalamus is known for its role as the
neuroendocrine stress mediator by regulating the hypothalamic-pituitary-adrenal (HPA) axis. However,
CRF signaling in extrahypothalamic brain regions also plays a key role in regulation of positive and
negative reinforcement of motivated behaviors in response to stressors through distinct CRF neural
circuits. Moreover, sex biases in CRF signaling may underlie female vulnerability to anxiety and
depression. Recently, we showed that the lateral ahebnula (LHb), an anti-reward brain region also
implicated in anxiety and depression, is a highly CRF-responsive brain region although the source of this
extrahypothalamic CRF neurotransmission to the LHb and its behavioral relevance in both sexes are still
unknown. Therefore, in this R21 grant proposal, we aim to explore the contribution of a newly identified
LHb neuronal subpopulation that expresses CRF (LHbCRF neurons) and provides a local inhibitory circuit
within the LHb in regulation of LHb activity and related anxiety-related behaviors in a sex- and circuit-
specific manner. Our specific aims are to identify the role of LHbCRF→LHb circuit in anxiety-related
behaviors and in CRF-dependent regulation of LHb. Our innovative experimental approach utilizing
mouse genetics, viral-based strategies, ex vivo optogenetics with electrophysiology, chemogenetics,
GCaMP calcium imaging, and behavior in female and male mice will enable us to uncover novel roles for
CRF in circuit-specific regulation of LHb function and LHb-related anxiety behaviors with implications
in stress-related disorders and female susceptibility to stress.
摘要
从下丘脑释放的促肾上腺皮质激素释放因子(CRF)以其作为促肾上腺皮质激素释放因子的作用而闻名。
神经内分泌应激介质通过调节下丘脑-垂体-肾上腺(HPA)轴。然而,在这方面,
下丘脑外脑区的CRF信号传导也在正性和负性调节中起关键作用。
通过不同的CRF神经元对应激源的激励行为进行负强化
电路.此外,CRF信号中的性别偏见可能是女性易受焦虑和焦虑影响的基础。
萧条最近,我们发现外侧无感觉核(LHb),一个抗奖赏的大脑区域,也
与焦虑和抑郁有关,是一个高度CRF反应的大脑区域,尽管这种反应的来源是
下丘脑外CRF神经传递到LHb及其在两性中的行为相关性仍然是
未知因此,在这项R21赠款提案中,我们的目标是探索一种新发现的
表达CRF(LHbCRF神经元)并提供局部抑制回路的LHb神经元亚群
在LHb内调节LHb活性和相关的焦虑相关行为,在性别和电路中,
具体方式。我们的具体目标是确定LHbCRF→LHb回路在焦虑相关的
行为和CRF依赖的LHb调节。我们的创新实验方法利用
小鼠遗传学,基于病毒的策略,具有电生理学的离体光遗传学,化学遗传学,
GCaMP钙成像,以及雌性和雄性小鼠的行为,将使我们能够发现新的作用,
CRF对LHb功能和LHb相关焦虑行为的回路特异性调节及其意义
与压力有关的疾病和女性对压力的敏感性。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Fereshteh S Nugent其他文献
Fereshteh S Nugent的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Fereshteh S Nugent', 18)}}的其他基金
Lateral habenula circuit dysregulation in mild traumatic brain injury
轻度创伤性脑损伤中的外侧缰核回路失调
- 批准号:
10323062 - 财政年份:2021
- 资助金额:
$ 22.78万 - 项目类别:
Effects of early life stress on synaptic function and DA signaling in the VTA
早期生活压力对 VTA 突触功能和 DA 信号传导的影响
- 批准号:
8886380 - 财政年份:2015
- 资助金额:
$ 22.78万 - 项目类别:
Effects of early life stress on synaptic function and DA signaling in the VTA
早期生活压力对 VTA 突触功能和 DA 信号传导的影响
- 批准号:
9057489 - 财政年份:2015
- 资助金额:
$ 22.78万 - 项目类别:
LTPGABA in the VTA and its Modulation by Opioids
VTA 中的 LTPGABA 及其阿片类药物的调节
- 批准号:
7276391 - 财政年份:2007
- 资助金额:
$ 22.78万 - 项目类别:
LTPGABA in the VTA and its Modulation by Opioids
VTA 中的 LTPGABA 及其阿片类药物的调节
- 批准号:
7423923 - 财政年份:2007
- 资助金额:
$ 22.78万 - 项目类别:
相似海外基金
Atomic Anxiety in the New Nuclear Age: How Can Arms Control and Disarmament Reduce the Risk of Nuclear War?
新核时代的原子焦虑:军控与裁军如何降低核战争风险?
- 批准号:
MR/X034690/1 - 财政年份:2024
- 资助金额:
$ 22.78万 - 项目类别:
Fellowship
Clinitouch-360: A digital health platform enabling robust end-to-end care of patients in Primary Care with depression and anxiety
Clinitouch-360:数字健康平台,可为初级保健中的抑郁和焦虑患者提供强大的端到端护理
- 批准号:
10098274 - 财政年份:2024
- 资助金额:
$ 22.78万 - 项目类别:
Collaborative R&D
Mental Health and Occupational Functioning in Nurses: An investigation of anxiety sensitivity and factors affecting future use of an mHealth intervention
护士的心理健康和职业功能:焦虑敏感性和影响未来使用移动健康干预措施的因素的调查
- 批准号:
10826673 - 财政年份:2024
- 资助金额:
$ 22.78万 - 项目类别:
Visual analysis system to detect and predict the signs of anxiety in healthcare
用于检测和预测医疗保健中焦虑迹象的视觉分析系统
- 批准号:
2902083 - 财政年份:2024
- 资助金额:
$ 22.78万 - 项目类别:
Studentship
Using generative AI combined with immersive technology to treat anxiety disorders
利用生成式人工智能结合沉浸式技术治疗焦虑症
- 批准号:
10109165 - 财政年份:2024
- 资助金额:
$ 22.78万 - 项目类别:
Launchpad
Healthy Young Minds: co-producing a nature-based intervention with rural High School students to promote mental well-being and reduce anxiety
健康的年轻心灵:与农村高中生共同开展基于自然的干预措施,以促进心理健康并减少焦虑
- 批准号:
MR/Z503599/1 - 财政年份:2024
- 资助金额:
$ 22.78万 - 项目类别:
Research Grant
"Flashforward" imagery and anxiety in young adults: Risk mechanisms and intervention development
年轻人的“闪现”意象和焦虑:风险机制和干预措施的发展
- 批准号:
MR/Y009460/1 - 财政年份:2024
- 资助金额:
$ 22.78万 - 项目类别:
Fellowship
How parents manage climate anxiety: coping and hoping for the whole family
父母如何应对气候焦虑:全家人的应对和希望
- 批准号:
DP230101928 - 财政年份:2024
- 资助金额:
$ 22.78万 - 项目类别:
Discovery Projects
An innovative biofeedback enhanced adaptive extended reality (XR) device to reduce perinatal pain and anxiety during and after childbirth
一种创新的生物反馈增强型自适应扩展现实 (XR) 设备,可减少分娩期间和分娩后的围产期疼痛和焦虑
- 批准号:
10097862 - 财政年份:2024
- 资助金额:
$ 22.78万 - 项目类别:
Collaborative R&D
Application name Phase Space - VR hypnotherapy as early intervention for anxiety in students and young people
应用程序名称 Phase Space - VR 催眠疗法作为学生和年轻人焦虑的早期干预
- 批准号:
10055011 - 财政年份:2023
- 资助金额:
$ 22.78万 - 项目类别:
Collaborative R&D