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了解行为相关的刺激如何在神经网络的活动中表现出来。在这项研究中，我们探讨了嗅觉系统中神经元回路的功能和行为之间的联系。当动物遇到新的气味或环境时，它们很快就会从被动呼吸转变为主动嗅觉。在人类中，帕金森氏症患者的嗅觉障碍会导致嗅觉任务缺陷。虽然嗅觉被认为在嗅觉的形成中起着重要的作用，但大脑皮层网络如何处理嗅觉过程中获得的信息还不清楚。我们在这项提案中描述的实验研究了产生动态皮质反应模式的细胞和电路级别的机制，这些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过程中产生不同的皮质群体反应。我们将结合体外钙成像和同步的多神经元电生理记录来阐明突触可塑性和电路结构在塑造皮质反应中的作用。这种机械性和详细的嗅觉皮层回路分析将为理解嗅觉信息在被动和主动行为状态下是如何处理的提供重要的框架。 与公共健康相关：尽管经过多年的研究，在了解大脑如何代表感觉信息方面取得了相当大的进展，但感觉输入、神经活动和行为之间的直接联系仍然难以捉摸。嗅觉是人类和动物的一种众所周知的行为，一次嗅觉就能提供嗅觉世界的快照。由于疾病导致的嗅觉障碍会导致嗅觉障碍。这项建议中的实验研究了微电路机制，通过这种机制，嗅觉过程中与行为相关的嗅觉输入模式反映在皮层神经活动的时空模式中。这类研究对于理解感觉输入如何在大脑皮层处理过程中转换以形成显著的知觉和行为反应至关重要。

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.