Learning in the main olfactory bulb

描述(申请人提供)：嗅觉系统有一项艰巨的任务，要区分复杂的气味，通常是由数百种挥发性成分组成的。该系统通过在嗅觉神经元(OSN)中表达~1000个嗅觉受体，解决了这一严峻的问题。每个OSN表达一个受体，所有表达相同受体的OSN将其轴突靶向相同的肾小球。因此，肾小球是一个功能活动单位，肾小球内的所有轴突都来自对挥发性成分的子集做出反应的OSN。虽然这一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征，但这种表征仍然很复杂，因为下游加工中心必须对~2000个肾小球的差异激活做出反应。主嗅球是负责处理肾小球激活所含信息的第一回路。它的组成包括二尖瓣和簇状细胞-投射神经元，其树突接受来自单个肾小球的输入，其轴突将信号传递到嗅皮层和中间神经元颗粒细胞，后者使树突状突触抑制二尖瓣细胞。这种电路被认为在处理气味质量信息方面发挥了重要作用，因为它能够对传递到嗅皮层的输入信号进行非线性滤波。在这项探索性的研究拨款申请中，我们提供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。在应用中，我们建议改进和验证一种从OB单位记录觉醒行为的技术，以测试二尖瓣细胞(MC)的气味响应性在Go-no Go气味辨别任务学习过程中发生变化的假设。PULBLIC健康相关性：项目叙述在人类中，嗅觉障碍在阿尔茨海默氏症(Doty，1991；Rawson，2000)、躁郁症(Hahn等人，2005年)和精神分裂症(Turetsky等人，2003年)等疾病中遇到。我们的工作是相关的，因为学习过程中OB活动的调节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.