Learning in the main olfactory bulb

描述（由申请人提供）：嗅觉系统具有区分通常由数百种挥发性组分组成的复杂气味的困难任务。该系统通过在嗅觉感觉神经元（OSN）中表达约1000个嗅觉受体来解决这个严格的问题。每个OSN表达一种受体，所有表达相同受体的OSN将其轴突靶向相同的肾小球。因此，肾小球是活动的功能单位，并且肾小球内的所有轴突都来自对挥发性组分的子集做出响应的OSN。虽然这种策略成功地以肾小球激活模式的形式形成了气味质量的肾小球表示，但这种表示仍然很复杂，因为下游处理中心必须响应约2000个肾小球的差异激活。主嗅球是负责处理肾小球激活中包含的信息的第一个回路。它的组成包括僧帽细胞和簇状细胞-投射神经元，其树突接收来自单个肾小球的输入，其轴突将信号传递到嗅觉皮层和中间神经元颗粒细胞，这些颗粒细胞在僧帽细胞上形成抑制性树-树突触。该电路被认为在处理气味质量信息中发挥重要作用，通过其执行传递到嗅觉皮层的输入信号的非线性滤波的能力。在这项探索性研究资助申请中，我们提出了令人兴奋的初步数据，表明当小鼠学习区分两种气味时，二尖瓣细胞对气味的反应会发生变化。在应用程序中，我们建议完善和验证的技术清醒的行为记录从OB单位来测试的假设，即气味反应的二尖瓣细胞（MC）的变化在学习过程中，在一个去-不去气味辨别任务。肺健康相关性：在人类中，嗅觉障碍在诸如阿尔茨海默氏症（Doty，1991;罗森，2000）、双相抑郁症（Hahn等人，2005）和精神分裂症（Turetsky等人，2003年）。我们的工作是相关的，因为在学习过程中OB活动的调制问题可能是这些病理的基础。

DESCRIPTION (provided by applicant): The olfactory system has the difficult task of discriminating between complex odors often made of hundreds of volatile components. The system solves this stringent problem by expressing ~1000 olfactory receptors in the olfactory sensory neurons (OSNs). Each OSN expresses one receptor, and all the OSNs expressing the same receptor target their axons to the same glomeruli. Thus, the glomerulus is a functional unit of activity and all axons within a glomerulus are from OSNs that respond to a subset of volatile components. While this strategy succeeds in forming a glomerular representation of odor quality in the form of a glomerular pattern of activation, this representation is still complex as downstream processing centers must respond to the differential activation of ~2000 glomeruli. The main olfactory bulb is the first circuit responsible for processing the information contained in glomerular activation. Its makeup includes the mitral and tufted cells - projection neurons whose dendrites receive input from a single glomerulus and whose axons transmit the signal to olfactory cortex } and interneurons } granule cells } that make inhibitory dendrodendritic synapses onto mitral cells. This circuit is thought to play an important role in processing odor quality information through its capability of performing nonlinear filtering of the input signal conveyed to the olfactory cortex. In this exploratory research grant application we present exciting preliminary data indicating that the responsiveness of mitral cells to odors changes as mice learn to differentiate between two odors. In the application we propose to refine and validate a technique for awake behaving recording from OB units to test the hypothesis that odor responsiveness of mitral cells (MCs) changes during learning in a go-no go odor discrimination task. PULBLIC HEALTH RELEVANCE: Project Narrative In humans disorders of the sense of smell are encountered in diseases such as Alzheimer's (Doty, 1991;Rawson, 2000), bipolar depression (Hahn et al., 2005) and schizophrenia (Turetsky et al., 2003). Our work is relevant because problems in the modulation of OB activity during learning could underlie some of these pathologies.