Inhibitory Processing and Social Learning in the Mouse Accessory Olfactory Bulb

项目摘要/摘要 化学感觉系统对人类和其他哺乳动物的社会行为有广泛的贡献， 包括小鼠，这是影响人类社会的疾病和紊乱的主要动物模型 功能。我们建议研究副嗅觉系统的神经回路，以便更好地 了解该系统如何从化学信息中提取信息并通知社会 行为。如果不能更好地理解这些过程，我们就有可能在 对涉及社会行为的疾病和障碍寻求新疗法的研究的解释。 兴奋性投射神经元被称为二尖瓣细胞(MCs)在第一神经回路的活动 副嗅觉系统，称为副嗅球(AOB)，强烈影响 生殖生理和社会行为。AOB二尖瓣细胞的活动受到几个 GABA能中间神经元的类型：球旁细胞、外颗粒细胞和内颗粒细胞 细胞(IGCs)。我们和其他人已经发现，AOB IGCs经历了经验依赖的可塑性 遵循化学感官的社会行为。我们将调查这样一种假设，即这些细胞 也许其他AOB中间神经元也参与了社会行为的可塑性。 我们将使用生理学技术的组合来研究细胞和突触 经历经验依赖性可塑性的AOB中间神经元的生理学。我们会研究 神经元间可塑性对化学感觉调节的影响。我们将使用靶向病毒转基因 体内、外选择性抑制AOB可塑性中间神经元活性的策略 用双光子钙成像和电生理方法测量群体AOB-MC活性 录音。这些实验将提供对以下假设的机械测试：经验- AOB中间神经元的依赖可塑性抑制获得性激活，但不是未获得性激活， 化学信号。最后，我们将调查可塑性AOB中间神经元在社会行为中的影响 在重复的社会接触中神经元激活的可塑性和全脑模式。 综合起来，这些研究将填补我们对化学感官信息理解的主要空白。 加工、依赖经验的可塑性和哺乳动物的社会行为。

Project Summary/Abstract Chemosensory systems contribute extensively to social behavior in humans and other mammals, including mice, a predominant animal model for diseases and disorders that impact human social function. We propose to study the neural circuitry of the accessory olfactory system in order to better understand how this system extracts information from chemical messages and informs social behavior. Without improved understanding of these processes, we risk making mistakes in the interpretation of studies seeking new therapies for diseases and disorders involving social behavior. The activity of excitatory projection neurons called mitral cells (MCs) in the first neural circuit in the accessory olfactory system, called the accessory olfactory bulb (AOB), strongly influences reproductive physiology and social behavior. AOB mitral cell activity is tightly controlled by several types of GABAergic interneurons: juxtaglomerular cells, external granule cells, and internal granule cells (IGCs). We and others have identified that AOB IGCs undergo experience-dependent plasticity following chemosensory social behaviors. We will investigate the hypothesis that these cells, and perhaps other AOB interneurons, are involved in social behavior plasticity. We will use a combination of physiological techniques to investigate cellular and synaptic physiology in AOB interneurons that undergo experience-dependent plasticity. We will study the impacts of interneuron plasticity on chemosensory tuning. We will use targeted viral transgenic strategies to selectively suppress activity of plastic AOB interneurons in vivo and ex vivo while measuring population AOB MC activity using 2-photon calcium imaging and electrophysiological recordings. These experiments will provide mechanistic tests of the hypothesis that experience- dependent plasticity in AOB interneurons suppresses activation by learned, but not unlearned, chemosignals. Finally, we will investigate the impacts of plastic AOB interneurons in social behavior plasticity and brain-wide patterns of neuronal activation during repeated social encounters. Combined, these studies will fill major gaps in our understanding of chemosensory information processing, experience-dependent plasticity, and mammalian social behavior.