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Contributions of hippocampal oxytocin receptors to social recognition

海马催产素受体对社会认可的贡献

基本信息

批准号：
10300447
负责人：
Amar Sahay
金额：
$ 42.25万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-11-15 至 2024-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10300447
关键词：
Address Adult Anxiety Attenuated Behavior Behavioral Biological Process Cells Cellular Compartment Analysis Code Communication Complex Data Disease Dorsal Excision Exposure to Feedback Female Fluorescent in Situ Hybridization Genetic Glean Goals Hilar Hippocampus (Brain)Image Impairment Lateral Light Link Mammals Mediating Memory Mental disorders Mus Neural Pathways Neuromodulator Neurons Noise Nucleus Accumbens Oxytocin Oxytocin Receptor Pathway interactions Pattern Pharmacology Prefrontal Cortex Process Prosencephalon Receptor Signaling Rewards Role Signal Transduction Social Behavior Social Discrimination Social Interaction Stimulus Testing Viral attenuation autism spectrum disorder avoidance behavior base cognitive process conditional mutant dentate gyrus design hippocampal pyramidal neuron insight male memory process neural circuit neuromechanism novel novel therapeutic intervention object recognition optogenetics population based receptor expression social social separation tool

项目摘要

Project Summary Social recognition in mammals is a complex biological process that necessitates communication between neural circuits mediating cognitive processes such as discrimination of social stimuli and those underlying expression of affiliation or avoidance behaviors. Circuit alterations that impair social discrimination, social interaction or linkage of social discrimination with social interaction may underlie social recognition deficits seen in autism spectrum disorders and other psychiatric disorders. One general mechanism by which distinct behaviors such as reward seeking, social exploration and discrimination of social stimuli are orchestrated is through the actions of neuromodulators such as oxytocin (OT). Although a growing number of studies have begun to shed light on oxytocin receptor (Oxtr) signaling in the nucleus accumbens, lateral septum and prefrontal cortex in social interaction, the contribution of Oxtrs in the hippocampus to social memory is not known. This proposal seeks to identify (i) fundamental circuit mechanisms by which hippocampal Oxtr signaling promotes discrimination of social stimuli and, (ii) the neural pathways that link these computations with circuits that subserve social interaction. Towards these goals, we will harness viral and mouse conditional genetic tools, optogenetics, cellular ensemble imaging and behavior to precisely manipulate hippocampal Oxtr signaling with unprecedented spatial and temporal control and determine its contributions to social recognition. Insights gleaned from the proposed studies will shed light on how an ancient neuromodulator like OT has evolved to utilize basic memory-processing circuit mechanisms to perform discrimination of social stimuli. The significance of the studies lies in its potential to illuminate fundamental neural mechanisms underlying previously unrecognized roles of hippocampal Oxtr signaling in social recognition. Ultimately, these mechanisms may guide novel therapeutic strategies for promoting social recognition in disorders in which it is impaired.

项目摘要哺乳动物的社会识别是一个复杂的生物学过程，需要它们之间的交流。神经回路介导的认知过程，如社会刺激的歧视和那些潜在的表示归属或回避行为。电路改变损害社会歧视，社会社会歧视与社会交往的相互作用或联系可能是社会承认缺陷的基础在自闭症谱系障碍和其他精神疾病中可见。一种通用机制，行为，如奖励寻求，社会探索和社会刺激的歧视是精心策划的，通过神经调节剂如催产素（OT）的作用。尽管越来越多的研究表明，开始揭示催产素受体（Oxtr）信号在脑桥核，外侧隔，虽然前额叶皮层在社会交往中起作用，但海马体中Oxtrs对社会记忆的贡献并不明显。知道的这项建议旨在确定（i）海马Oxtr 信号促进社会刺激的歧视，（ii）连接这些计算的神经通路有着促进社会互动的电路为了实现这些目标，我们将利用病毒和小鼠条件遗传工具，光遗传学，细胞整体成像和行为，以精确操纵海马Oxtr 信号与前所未有的空间和时间控制，并确定其对社会的贡献识别.从拟议的研究中收集到的见解将阐明一种古老的神经调节剂，如 OT已经发展到利用基本的记忆处理电路机制来执行社会识别。刺激。这些研究的意义在于它有可能阐明基本的神经机制海马Oxtr信号在社会识别中的潜在作用。最后，这些机制可以指导新的治疗策略，以促进社会承认的障碍，它是受损的。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Hippocampal oxytocin receptors are necessary for discrimination of social stimuli.

DOI：
10.1038/s41467-017-02173-0
发表时间：
2017-12-08
期刊：
Nature communications
影响因子：
16.6
作者：
Raam T;McAvoy KM;Besnard A;Veenema AH;Sahay A
通讯作者：
Sahay A

Corticosterone inhibits GAS6 to govern hair follicle stem-cell quiescence.

DOI：
10.1038/s41586-021-03417-2
发表时间：
2021-04
期刊：
Nature
影响因子：
64.8
作者：
Choi S;Zhang B;Ma S;Gonzalez-Celeiro M;Stein D;Jin X;Kim ST;Kang YL;Besnard A;Rezza A;Grisanti L;Buenrostro JD;Rendl M;Nahrendorf M;Sahay A;Hsu YC
通讯作者：
Hsu YC

A dentate gyrus-CA3 inhibitory circuit promotes evolution of hippocampal-cortical ensembles during memory consolidation.