Synaptic Processes Mediating Cortical Odor Coding

描述(申请人提供)：嗅觉信息由嗅球小球以组合的方式编码，它们分别代表不同气味的不同化学特征。这些信息被传输到梨状皮质，在那里它被推定为形成这些离散信号的组合，并导致气味感知。这项提议的重点是了解梨状皮质细胞如何整合来自嗅球的信息。我将试图通过询问有关梨状皮质神经元的整合特性的具体问题，来获得有关嗅觉信息在大脑中是如何呈现的基本见解。这里提出的实验将确定梨状皮质单个细胞的肾小球输入的数量(目标1)。我将确定激活一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协同输入的组合如何整合到梨状皮质神经元中(目标2)。我还将确定高级大脑区域如何影响梨状皮质神经元的整合特性。我会特别问，从眼眶前额叶皮质到梨状皮质神经元的输入是否会改变来自灯泡的感觉输入的影响(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用来处理感觉刺激的解剖学和生理学策略。这些信息对于了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理查德·阿克塞尔博士和史蒂文·西格尔鲍姆博士的实验室举行。阿克塞尔博士对嗅觉的分子、细胞和电路基础进行了广泛的研究。西格尔鲍姆博士取得了一些关键发现，阐明了离子通道的调节和表达如何影响神经回路和改变行为。阿克塞尔博士和西格尔鲍姆博士在向独立过渡期间指导研究员方面都有杰出的记录。相关性(参见说明)：中央嗅觉系统是最容易处理的大脑回路之一，允许对大脑如何处理感觉信息进行基本的洞察。对这些过程的清楚了解对于了解大脑在健康和疾病中的功能至关重要。例如，气味感知问题是严重神经系统疾病的早期指标，包括帕金森氏症和阿尔茨海默氏症。

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.