Olfactory circuits that control behavior

描述(由申请者提供)：人类的行为由感官输入通过鲜为人知的机制来控制。调节触觉、味觉、视觉、嗅觉和听觉的感觉系统激活了大脑中处理环境信息的专用神经回路。这些神经回路通过瞄准特定的大脑深层结构来控制行为。然而，目前还不清楚具体的感觉输入是如何通过这些大脑结构来控制行为的。了解神经回路如何调节行为是神经科学领域的基本目标，而与攻击、恐惧和其他社会行为相关的神经回路功能障碍是许多人类神经疾病的特征。在这里，我们研究小鼠的嗅觉回路，作为一个有价值的模型，以了解感觉系统如何调节行为。在老鼠身上，信息素和捕食者气味是高度可控的刺激，可以触发强大的、遗传编程的行为反应。在初步数据中，我们确定了许多控制特定老鼠行为的气味，并已做好准备研究涉及交配、攻击、恐惧和厌恶的神经回路。我们将结合分子生物学、神经回路分析和小鼠遗传学来研究小鼠嗅觉系统是如何调节行为的。我们将(1)识别控制老鼠行为的信息素，(2)识别检测信息素的嗅觉受体，(3)绘制信息素激活的神经回路图。产生一组信息素和气味，激活不同的硬连接神经回路和本能行为，将为理解构成社交行为基础的大脑神经回路的基本功能和组织提供宝贵的工具箱。我们工作的最终目标是了解高阶大脑结构中的神经回路如何组织感觉输入来控制行为。了解神经回路在健康状态下如何工作的一般原理为理解人类疾病潜在的功能障碍提供了关键基础。

DESCRIPTION (provided by applicant): Human behavior is controlled by sensory input through poorly understood mechanisms. Sensory systems that mediate touch, taste, vision, smell, and hearing activate dedicated neural circuits in the brain that process environmental information. These neural circuits control behavior by targeting particular deep brain structures. However, it remains unknown how specific sensory inputs are routed through these brain structures to control behavior. Understanding how neural circuits function to regulate behavior is a basic goal of the neuroscience field, and dysfunction of neural circuits associated with aggression, fear, and other social behaviors is characteristic of numerous human neurological disorders. Here, we study olfactory circuits in mice as a valuable model for understanding how a sensory system can regulate behavior. In mice, pheromones and predator odors are highly controllable stimuli that trigger robust, genetically programmed behavioral responses. In preliminary data, we identified numerous odors that control specific mouse behaviors, and are well poised to study neural circuits involved in mating, aggression, fear, and aversion. We will use a combination of molecular biology, neural circuit analysis, and mouse genetics to study how the mouse olfactory system regulates behavior. We will (1) identify pheromones that control mouse behavior, (2) identify olfactory receptors that detect pheromones, and (3) chart neural circuits activated by pheromones. Generating a collection of pheromones and odors that activate different hard-wired neural circuits and instinctive behaviors will provide a valuable toolbox for understanding the basic function and organization of neural circuits in the brain that underlie social behavior. The ultimate goal of our work is to understand how neural circuits in higher order brain structures organize sensory inputs to control behavior. Understanding general principles of how neural circuits function in the healthy state provides a critical foundation for understanding dysfunction underlying human disease.