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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：
10434157
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 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10434157
关键词：
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 Goals Halorhodopsins Hippocampus (Brain)Institution Interneurons Label Laboratories Lead 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 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 neuronal circuitry novel strategies optogenetics 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，具有信息整合和神经支配功能