Synaptic Processes Mediating Cortical Odor Coding

描述（由申请人提供）：嗅觉信息由嗅球小球以组合方式编码，嗅球小球单独代表不同气味剂的不同化学特征。这些信息被传递到梨状皮质，在那里它被认为是这些离散信号的组合，并导致气味感知。本研究的重点是了解梨状皮质细胞如何整合嗅球信息。我将试图通过提出关于梨状皮质神经元整合特性的具体问题，来获得嗅觉信息在大脑中是如何表达的基本见解。这里提出的实验将确定到梨状皮质中的单个细胞的肾小球输入的数量（目的1）。我将确定激活单个梨状皮质神经元需要多少个肾小球，以及来自不同肾小球的共同活动输入组合如何整合到梨状皮质神经元中（目的2）。我还将确定更高的大脑区域如何影响梨状皮质神经元的整合特性。我将特别询问来自眶额皮质的输入到梨状皮质神经元是否会改变来自球的感觉输入的影响（目标3）。这些实验将需要使用新技术，这些技术将在指导阶段开发，并在授标的指导阶段和独立阶段广泛使用。这些数据将阐明中枢神经回路处理感官刺激所采用的解剖学和生理学策略。这些信息对于理解中枢神经系统的正常和病理状态都是必不可少的。该奖项的指导阶段将在哥伦比亚大学的Richard阿克塞尔博士和Steven Siegelbaum博士的实验室进行。阿克塞尔博士广泛研究了嗅觉的分子、细胞和回路水平基础。Siegelbaum博士的重要发现说明了离子通道的调节和表达如何影响神经回路并改变行为。阿克塞尔博士和西格尔鲍姆博士在指导研究员向独立过渡方面都有杰出的记录。相关性（参见说明）：中央嗅觉系统是最易处理的大脑回路之一，它允许对大脑如何处理感觉信息的基本见解。清楚地了解这些过程对于了解健康和疾病中的大脑功能至关重要。例如，气味感知问题是严重神经系统疾病的早期指标，包括帕金森病和阿尔茨海默病。

DESCRIPTION (provided by applicant): Olfactory information is encoded in a combinatorial fashion by olfactory bulb glomeruli, which individually represent distinct chemical features of different odorants. This information is transmitted to the piriform cortex, where it is presumed to form combinations of these discrete signals, and leads to an odor percept. The focus of this proposal is to understand how cells in piriform cortex integrate information from olfactory bulb. I will attempt to gain fundamental insights into how olfactory information is represented in the brain by asking specific questions about the integrative properties of piriform cortex neurons. The experiments proposed here will determine the number of glomerular inputs onto single cells in piriform cortex (Aim 1). I will determine how many glomeruli are required to activate a single piriform cortex neuron and how combinations of coactive inputs from different glomeruli are integrated in piriform cortex neurons (Aim 2). I will also determine how higher brain areas affect the integration properties of piriform cortex neurons. I will specifically ask whether inputs onto piriform cortex neurons from orbitofrontal cortex alter the impact of sensory inputs from the bulb (Aim 3). These experiments will require the use of new techniques that will be developed during the mentored phase and used extensively during both the mentored and independent phases of the award. These data will shed light on the anatomical and physiological strategies employed by central neural circuits to process sensory stimuli. Such information is essential to understanding both the normal and pathological states of the central nervous system. The mentored phase of this award will take place in the laboratories of Dr. Richard Axel and Dr. Steven Siegelbaum at Columbia University. Dr. Axel has extensively studied the molecular, cellular and circuit-level basis for olfaction. Dr. Siegelbaum has made key discoveries illustrating how regulation and expression of ion channels affect neural circuits and alter behavior. Both Dr. Axel and Dr. Siegelbaum have distinguished track records in mentoring fellows through the transition to independence. RELEVANCE (See instructions): The central olfactory system is one of the most tractable brain circuits, permitting fundamental insights into how the brain processes sensory information. A clear understanding of these processes is crucial for an understanding of brain function in health and disease. For example, problems with odor perception are early indicators for serious neurological diseases, including Parkinson's and Alzheimers' Disease.