CIRCUIT MECHANISMS SHAPING OLFACTORY CORTICAL RESPONSES DURING PASSIVE AND ACTIVE

描述（由申请人提供）：感官研究的一个中心问题是理解行为相关刺激如何在神经网络的活动中表现出来。在这个提议中，我们探索神经回路功能和嗅觉系统行为之间的联系。当动物遇到一种新的气味或环境时，它们会迅速从被动呼吸转变为主动嗅探。在人类中，帕金森氏症患者的嗅觉受损会导致嗅觉任务缺陷。尽管人们认为嗅探在嗅觉感知的形成中起着重要作用，但尚不清楚皮层网络如何处理嗅探过程中获得的信息。我们在本提案中描述的实验研究了产生动态皮层反应模式的细胞和回路水平机制，这些反应模式反映了被动呼吸与主动嗅探期间获得的输入。我们的初步数据表明，嗅球输入的短期突触可塑性和局部神经元间微回路协同作用，在被动呼吸和主动嗅探期间产生不同的皮层群体反应。我们将结合体外钙成像和同时，多神经元，电生理记录来阐明突触可塑性和电路结构在形成皮层反应中的作用。这种机制和详细的分析嗅觉皮层电路将为理解被动和主动行为状态下嗅觉信息的处理提供一个重要的框架。

DESCRIPTION (provided by applicant): A central issue in sensory research is understanding how behaviorally relevant stimuli are represented in the activity of neural networks. In this proposal, we explore the links between the function of neuronal circuits and behavior in the olfactory system. When animals encounter a novel odorant or environment they quickly transition from passive respiration to active sniffing. In humans, impaired sniffing in Parkinson's patients leads to olfactory task deficits. Although sniffing is proposed to play an important role in the formation of olfactory percepts, it is not known how cortical networks process information acquired during sniffing. The experiments we describe in this proposal investigate the cellular and circuit-level mechanisms that produce dynamic cortical response patterns that are reflective of input obtained during passive respiration versus active sniffing. Our preliminary data suggests that short-term synaptic plasticity in olfactory bulb inputs and local interneuron microcircuits act synergistically to produce differential cortical population responses during passive respiration versus active sniffing. We will use a combination of in vitro calcium imaging and simultaneous, multi-neuron, electrophysiological recording to elucidate the roles of synaptic plasticity and circuit architecture in shaping cortical responses. Such a mechanistic and detailed analysis olfactory cortical circuitry will provide an important framework for understanding how olfactory information is processed during passive and active behavioral states. PUBLIC HEALTH RELEVANCE: Despite years of research, and considerable progress in understanding how the brain represents sensory information, direct links between sensory input, neural activity and behavior remain elusive. Sniffing is a well-known behavior in humans and animals and a single sniff provides a snapshot of the olfactory world. Impaired sniffing due to disease can result in olfactory perceptual deficits. The experiments in this proposal investigate the microcircuit mechanisms by which behaviorally relevant patterns of olfactory input during sniffing are reflected in the spatiotemporal patterns of cortical neural activity. Such studies are critical for understanding how sensory input is transformed during cortical processing to form salient percepts and behavioral responses.