Olfactory-limbic connection: from scents to behavior

社会行为，从冲突(如攻击性、杀婴)到合作(如交配、母婴互动)，可以在所有有性繁殖的动物物种中观察到，对它们的健康、生存和繁殖至关重要。这些行为是本能的，因为它们可以在没有事先训练的情况下在存在特定的感觉刺激(主要是嗅觉/信息素)的情况下表现出来。然而，对编码这些行为反应的潜在神经元回路知之甚少。因此，我们建议定义嗅觉介导的社会行为的分子、细胞和神经基础--从电路特征到行为相关性。具体地说，我们的目标是确定社交信号如何在嗅球中编码，并传递到边缘系统中被认为对社交行为重要的不同中央大脑区域。接下来，我们将研究边缘系统中表达神经递质GABA和芳香酶的特定神经元是如何处理这些信号的，并确定它们被激活的特定社交行为。我们将使用多层次的方法，结合体内双光子和显微内窥镜记录、基于病毒的电路追踪、基因打靶和行为测试来阐明嗅觉回路的解剖-生理特性，并探讨它们在控制社会行为中的功能作用。社会行为是千篇一律的，因此在发育上是硬连接的，这使得它们可以通过分子遗传学方法来表征潜在的神经回路。我们将执行三个既独立又相互联系的具体目标。作为第一步，我们将使用病毒示踪剂识别以杏仁内侧核和终纹床核中GABA能和芳香酶表达神经元为靶点的嗅球神经回路，并确定支配这一特定神经通路的嗅球神经元的分子身份。作为第二步，我们将使用体内钙成像技术研究这些嗅球神经元对引起特定社会行为的化学信号的反应的分子范围。最后，我们将对活体内不同行为背景下GABA和芳香酶阳性神经元的活性进行功能表征。综上所述，对控制明确的嗅觉驱动的先天行为的神经通路的详细研究将为理解大脑如何编码复杂的行为提供一个重要的里程碑。

Social behaviors, ranging from conflictive (e.g. aggression, infanticide) to cooperative (e.g. mating, mother-pup interaction), can be observed in all sexually reproducing animal species and are crucial for their health, survival, and reproduction. These behaviors are instinctual in the sense that they can be displayed without prior training in the presence of specific sensory stimuli, largely olfactory/pheromonal in nature. However, little is known about the underlying neuronal circuits encoding these behavioral responses. Therefore, we propose to define the molecular, cellular and neural basis of olfactory-mediated social behaviors – from circuit characterization to behavioral relevance. Specifically, we aim to determine how social signals are encoded in the olfactory bulb and relayed to different central brain areas in the limbic system that are considered important for social behavior. Next, we will study how these signals are processed by specific neurons in the limbic system that express the neurotransmitter GABA and the enzyme aromatase and identify specific social behaviors in which they are activated. We will use a multi-level approach combining two-photon and microendoscopic recordings in vivo, virus-based circuit tracing, gene targeting, and behavioral testing to elucidate the anatomical-physiological properties of olfactory circuits and to address their functional role in the control of social behavior. Social behaviors are stereotyped and thus developmentally hard-wired, making them accessible to molecular genetic approaches to characterize the underlying neural circuits. We will execute three specific aims that are independent but interconnected. As a first step, we will identify the neural circuits from the olfactory bulb that target GABAergic and aromatase-expressing neurons in the medial amygdala and bed nucleus of the stria terminalis using viral tracers and determine the molecular identity of olfactory bulb neurons innervating this specific neural pathway. As a second step we will investigate the molecular range of these olfactory bulb neurons in response to chemosignals eliciting specific social behaviors using calcium imaging in vivo. Finally, we will functionally characterize the activity of GABA and aromatase positive neurons in different behavioral contexts in vivo. Taken together, this detailed study of neural pathways controlling well-defined olfactory-driven innate behaviors will provide an important landmark for understanding how the brain encodes complex behavior.