权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Interneurons differentially regulate discrete pathways from ventral hippocampus

中间神经元差异调节腹侧海马的离散通路

基本信息

批准号：
10634672
负责人：
Jennifer Donegan
金额：
$ 24.9万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10634672
关键词：
Affect Alzheimer&apos s Disease Anatomy Animals Area Attenuated Award BRAIN initiative Behavior Behavioral Binding Proteins Brain Diseases Brain region Cells Chronic Chronic stress Cognition Complex Development Plans Disease ES Cell Line Educational workshop Electrophysiology (science)Emotions Ensure Equilibrium Fiber Functional disorder Funding Genetic Goals Halorhodopsins Hippocampus Institution Intellectual functioning disability Interneurons Label Laboratories LoxP-flanked allele Maps Medial Mediating Mental disorders Mentors Metabolic Modeling Mus Neurobehavioral Manifestations Neurodegenerative Disorders Neurodevelopmental Disorder Neurons Neuropeptides Neurophysiology - biologic function Nucleus Accumbens Parkinson Disease Parvalbumins Pathway interactions Pattern Photometry Physiology Population Predisposing Factor Prefrontal Cortex Prevention Prevention strategy Process Pyramidal Cells Regulation Reporter Research Research Personnel Rhodopsin Risk Factors Rodent Model Schizophrenia Scientist Somatostatin Stress Structure Substance abuse problem Symptoms Synapses Synaptic Cleft Techniques Testing Time Training Transplantation Viral Vector Virus Vocational Guidance Work autism spectrum disorder career development cold stress effective therapy experimental study extracellular hippocampal pyramidal neuron improved in vivo information processing insight meetings nervous system disorder neural circuit neurobiological mechanism neuron component neuronal circuitry novel strategies novel therapeutic intervention optogenetics postsynaptic presynaptic psychological stressor reconstitution response skills stressor symposium treatment strategy

项目摘要

Hippocampal microcircuits are comprised of excitatory pyramidal cells, which integrate information and innervate downstream brain regions, and inhibitory interneurons, which function locally to regulate pyramidal cell activity and synchronicity. In the ventral hippocampus (vHipp), microcircuit dysfunction has been associated with a variety of neurological disorders, including neurodegenerative diseases, neurodevelopmental disorders, and psychiatric illnesses. Previous work has demonstrated that vHipp pyramidal cells differentially regulate schizophrenia-like behaviors depending on their downstream target. Similarly, unique classes of inhibitory interneurons (namely parvalbumin (PV)-positive and somatostatin(SST)-positive) also differently regulate schizophrenia-like behaviors. Therefore, the hypothesis of the current proposal is that PV- and SST-positive interneurons differentially regulate the function of ventral hippocampus pyramidal cells depending on their projection target. In the first aim, mammalian reconstitution across synaptic partners (mGRASP) will be used to test the hypothesis that PV- and SST-positive interneurons differentially innervate vHipp pyramidal cells depending on their target (i.e. the NAc or mPFC). In the second aim, fiber photometry, in vivo electrophysiology, and optogenetics will be used to test the functional regulation of NAc vs mPFC projecting vHipp neurons by PV- and SST-positive interneurons. Aim 3 will determine if microcircuit anatomy and function are altered by chronic stress, a predisposing factor for many neurological disorders. In line with the goals of the BRAIN Initiative, the results will provide insight into basic principles of neural circuit function and may lead to new strategies for the treatment and prevention of devastating neurological disorders. My long-term goal is to become an independent scientist that studies the neurobiological mechanisms underlying psychiatric disorders so that new and more effective treatments can be developed. The research plan described above will be supplemented by a career development plan that will allow me to gain the skills necessary to achieve this goal. Specifically, I have assembled a team of mentors from both in and outside of my institution to provide scientific training and career guidance. Further, I will attend local and national conferences, workshops, and meetings to enhance my training and ensure that I gain the skills requisite of an independent investigator. Together, this award will provide me with scientific training and career development opportunities, and importantly it will allow me to establish my own, independent line of research, which will focus on the effect of chronic stress on vHipp microcircuits.

海马微回路由兴奋性锥体细胞组成，这些细胞整合信息并支配下游脑区和抑制性中间神经元，其功能是局部调节锥体细胞活动和同步性。在腹侧海马体（vHipp）中，微回路功能障碍与各种神经系统疾病，包括神经退行性疾病、神经发育障碍和精神疾病。以前的工作已经证明vHipp锥体细胞差异调节类似精神分裂症的行为取决于他们的下游目标。类似地，独特的抑制类中间神经元（即小白蛋白（PV）阳性和生长抑素（SST）阳性）也不同地调节类似精神分裂症的行为因此，当前提案的假设是PV和SST阳性 interneurons差异调节腹侧海马锥体细胞的功能，这取决于它们的投射目标在第一个目标中，将使用跨突触伴侣的哺乳动物重建（mGRASP）来检验PV和SST阳性中间神经元对vHipp锥体细胞有差异性神经支配的假设这取决于它们的目标（即NAc或mPFC）。在第二个目标中，纤维光度测定，体内电生理学，和光遗传学将用于测试PV-1对NAc与mPFC投射vHipp神经元的功能调节。和SST阳性中间神经元。目标3将确定微电路解剖结构和功能是否因慢性压力是许多神经系统疾病的诱发因素。根据BRAIN倡议的目标，研究结果将提供深入了解神经回路功能的基本原理，并可能导致新的战略，治疗和预防毁灭性的神经系统疾病。我的长期目标是成为一名研究神经生物学机制的独立科学家潜在的精神疾病，以便开发新的和更有效的治疗方法。研究计划我将通过职业发展计划来补充上述内容，使我能够获得技能必须实现这一目标。具体来说，我已经组建了一个导师团队，来自我的内部和外部。提供科学培训和职业指导。此外，我将参加地方和国家会议，讲习班和会议，以加强我的培训，并确保我获得独立工作所需的技能。调查员总之，这个奖项将为我提供科学培训和职业发展的机会，重要的是，这将使我能够建立自己的独立研究路线， vHipp微电路的慢性压力。