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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认知是一个复杂的生物过程，需要神经回路调节认知过程，如对社会刺激和潜在刺激的辨别表达从属关系或回避行为。损害社会歧视、社会歧视的巡回修改社会歧视与社会互动的相互作用或联系可能是社会认可度缺失的基础可见于自闭症谱系障碍和其他精神障碍。一种通用的机制，通过它不同的诸如寻求奖励、社会探索和社会刺激歧视等行为是精心策划的通过催产素(OT)等神经调节剂的作用。尽管越来越多的研究已经开始阐明伏核、外侧隔核和下丘脑中的催产素受体(OXTR)信号在社会互动中，海马区Oxtrs对社会记忆的贡献为人所知。这项建议试图确定(I)海马OXTR 信号传递促进对社会刺激的辨别，以及(Ii)连接这些计算的神经通路有辅助社交互动的电路。为了实现这些目标，我们将利用病毒和老鼠条件遗传工具、光遗传学、细胞集合成像和行为精确操纵海马区OXTR 以前所未有的空间和时间控制发送信号，并确定其对社会的贡献承认。从拟议的研究中收集的见解将有助于阐明一种古老的神经调节剂是如何 OT已经发展到利用基本的记忆处理电路机制来执行社会辨别刺激物。这些研究的意义在于它有可能阐明基本的神经机制。之前未被认识到的海马区OXTR信号在社会识别中的作用。最终，这些机制可能会指导新的治疗策略，以促进精神障碍的社会认可而这一点却受到了损害。

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.