Interneurons differentially regulate discrete pathways from ventral hippocampus

海马区微电路由兴奋性锥体细胞组成，它们整合信息和神经支配。 下游脑区和抑制性中间神经元，它们在局部发挥调节锥体细胞活动的功能 和同步性。在腹侧海马区(VHipp)，微回路功能障碍与 各种神经疾病，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锥体细胞对 精神分裂症样的行为取决于它们的下游目标。同样，独特的抑制性类别 中间神经元(即小白蛋白(PV)阳性和生长抑素(SST)阳性)也有不同的调节作用 精神分裂症样行为。因此，目前提议的假设是PV和SST阳性 中间神经元对腹侧海马锥体细胞功能的不同调节 投射目标。在第一个目标中，跨突触伙伴的哺乳动物重构(MGRASP)将用于 验证PV和SST阳性中间神经元分化支配vHipp锥体细胞的假说 取决于他们的目标(即NAC或mPFC)。在第二个目标中，纤维光度学，活体电生理学， 并将利用光遗传学来测试PV-1对NAC和mPFC投射vHipp神经元的功能调节。 和SST阳性中间神经元。目标3将确定慢性疾病是否会改变微电路的解剖和功能 压力，许多神经疾病的易感因素。与大脑倡议的目标一致， 研究结果将提供对神经回路功能的基本原理的洞察，并可能导致新的策略 治疗和预防破坏性神经疾病。 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 潜在的精神障碍，以便可以开发新的、更有效的治疗方法。研究计划 如上所述，我将得到职业发展计划的补充，这将使我能够获得技能 这是实现这一目标所必需的。具体地说，我组建了一个由来自我的内外的导师组成的团队 机构提供科学的培训和职业指导。此外，我还将参加地方和国家会议， 研讨会和会议，以加强我的培训并确保我获得独立工作人员所需的技能 调查员。总而言之，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，重点是影响 慢性应激对vHipp微电路的影响。

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.