A potential novel role for hippocampal subregion ventral CA2 in sociability

项目摘要/摘要 群居动物，包括人类和啮齿动物，有一种与生俱来的动力去寻找并与之建立联系 有利于它们生存的同种特异体。这种对社会接触的驱动力在多个人类精神病患者中减弱 以及神经障碍，包括自闭症谱系障碍、精神分裂症和抑郁症。这个 调节社交能力的基本大脑结构和回路，定义为对社交的偏好和渴望 随着研究人员为基于电路的干预寻找新的靶点，相互作用正在进行密集的研究 这些障碍。 海马体是一个大脑结构，在记忆和行为中起着至关重要的作用。显示为扩展的 “C”形结构在啮齿动物中，海马体可以沿着其纵向(背腹)进一步确定。 轴心。背侧(DHPC)和腹侧(VHPC)海马区被认为具有不同的功能作用， DHPC调节包括空间导航和语境记忆在内的认知功能，并影响vHPC 情绪处理和焦虑。抑制vHPC可增加啮齿动物的社交能力，这可能是由于减少了 焦虑。目前尚不清楚海马体是否可以独立于焦虑影响社交能力。 此外，海马体还可沿着其分支被细分为角质区CA1-CA4 横轴。最近，海马区CA2已成为一种重要的社会调节因子。 识别记忆(SRM)和行为。在海马体中，基因的全球敲除 在CA2中表达会导致SRM、社交攻击性(SA)和社交能力下降。相比之下，虽然急性或 慢性抑制CA2背侧区(DCA2)会减少SRM和SA，但不会改变社交能力。 鉴于dCA2在社会记忆和行为中的重要性，以及vHPC在情绪调节中的作用，我 假设腹侧CA2(VCA2)可能调节社交能力。我的初步结果显示急性 药物遗传抑制vCA2导致社交能力显著降低，而不伴随 焦虑的变化。我将通过两个目标来验证我的假设，即vCA2在社交中的作用：首先，我将探索 VCA2在社会和非社会行为中的必要性和充分性(目标1)。然后我会调查 潜在的vCA2投射和活动对vCA2的S在社会行为中的作用是重要的(目标2)。一起， 这些结果将扩大对构成社交能力基础的大脑回路的理解，并有可能识别 VCA2作为治疗社会兴趣降低的疾病的新靶点。

Project Summary/Abstract Social animals, including humans and rodents, have an inherent drive to seek out and create bonds with conspecifics that benefit their survival. This drive for social contact is diminished in multiple human psychiatric and neurological disorders, including autism spectrum disorders, schizophrenia, and depression. The underlying brain structures and circuits that mediate sociability, defined as the preference and desire for social interaction, are under intense investigation as researchers seek new targets for circuit-based interventions of these disorders. The hippocampus is a brain structure with crucial roles in memory and behavior. Appearing as an extended “C”-shaped structure in rodents, the hippocampus can be further defined along its longitudinal (dorsoventral) axis. The dorsal (dHPC) and ventral (vHPC) hippocampus are proposed to have different functional roles, with dHPC regulating cognitive functions including spatial navigation and contextual memory, and vHPC influencing emotional processing and anxiety. Inhibition of vHPC increases sociability in rodents, likely due to decreased anxiety. Whether the hippocampus can influence sociability independently of anxiety remains unclear. The hippocampus can be additionally subdivided into the Cornu Ammonis subfields CA1-CA4 along its transverse axis. The hippocampal subregion CA2 has recently emerged as a crucial regulator of social recognition memory (SRM) and behavior. Global knockout of genes that, in the hippocampus, are exclusively expressed in CA2 results in decreased SRM, social aggression (SA), and sociability. In contrast, while acute or chronic inhibition of the dorsal region of CA2 (dCA2) reduce SRM and SA, it does not alter sociability. Given the importance of dCA2 in social memory and behavior, and the role of vHPC in emotional regulation, I hypothesize that ventral CA2 (vCA2) may regulate sociability. My preliminary results indicate that acute pharmacogenetic inhibition of vCA2 results in a significant reduction in sociability, without a concomitant change in anxiety. I will test my hypothesis of a role for vCA2 in sociability through two aims: first, I will probe the necessity and sufficiency of vCA2 in social- and non-social behaviors (Aim 1). I will then investigate the underlying vCA2 projections and activity that are important for vCA2’s role in social behavior (Aim 2). Together, these results will expand understanding of the brain circuits that underlie sociability, and potentially identify vCA2 as a new target for treatment of disorders with reduced social interest.