Olfactory Glomeruli: Cellular and Network Mechanisms

描述（由申请人提供）：肾小球是嗅觉通路中突触整合的起始部位。来自表达相同气味受体的嗅觉受体神经元的嗅神经（ON）轴突投射到主嗅球中的相同的一个或几个肾小球，在那里它们与二尖瓣/簇状细胞（MC/TC）和局部肾小球（JG）中间神经元的顶端树突突触。因此，每个肾小球都可以被认为是处理感觉输入的功能单位。我们假设，每个肾小球是由一个小套刻板的神经元亚型，专门组织执行离散的网络操作。这些网络操作确定从ON端子到MC和TC（MOB的输出神经元）的传递函数。我们进一步假设这些肾小球传递功能主要作用于每个肾小球中ON活性的大小。在肾小球网络的下游发生跨肾小球系综的模式化活性的分析。 目的1将确定JG神经元突触联系的递质和受体。目的2-4测试关于三种特定肾小球功能和执行这些操作的细胞网络机制的假设。目的2将（i）检验突触前DA能和GABA能JG细胞通过改变Ca ~（2+）介导的递质释放来抑制ON终末的假设，和（ii）将使用体内Ca ~（2+）成像和气味刺激来检验突触前抑制功能缩放肾小球输出的动态响应范围的假设。目的3将使用体外和体内实验来验证这一假设，即有节奏地爆发外部簇状细胞的功能，以放大和同步肾小球输出反应的气味刺激。目的4将验证短轴突JG细胞介导局部肾小球间侧抑制的假设。这种侧抑制提供了肾小球间对比度增强，其与每个肾小球的ON输入的幅度成比例。 这一更新申请建立在上一个奖项的成就基础上，并使用新的方法来阐明启动气味计算的神经网络的组织和功能。

DESCRIPTION (provided by applicant): The glomeruli are the initial site of synaptic integration in the olfactory pathway. Olfactory nerve (ON) axons from olfactory receptor neurons expressing the same odorant receptor project to the same one or few glomeruli in the main olfactory bulb, where they synapse on the apical dendrites of mitral/tufted cells (MC/TCs) and local juxtaglomerular (JG) interneurons. Each glomerulus, hence, can be considered a functional unit for processing sensory input. We hypothesize that each glomerulus is comprised of a small set of stereotyped neuron sub-types, specifically organized to perform discrete network operations. These network operations determine the transfer function from ON terminals to MCs and TCs, the output neurons of MOB. We further hypothesize that these glomerular transfer functions operate primarily on the magnitude of ON activity in each glomerulus. Analysis of patterned activity across the glomerular ensemble occurs downstream of the glomerular network. Aim 1 will identify the transmitters and receptors underlying the synaptic relationships of JG neurons. Aims 2-4 test hypotheses about three specific glomerular functions and the cellular-network mechanisms that perform these operations. Aim 2 will (i) test the hypothesis that DA- and GABAergic JG cells presynaptically inhibit ON terminals by altering Ca2+-meditaed transmitter release, and (ii) will use in vivo Ca2+ imaging and odor stimuli to test the hypothesis that presynaptic inhibition functions to scale the dynamic response range of glomerular output. Aim 3 will use in vitro and in vivo experiments to test the hypothesis that rhythmically bursting external tufted cells function to amplify and synchronize glomerular output responses to odor stimulation. Aim 4 will test the hypothesis that short axon JG cells function to mediate local, interglomerular lateral inhibition. This lateral inhibition provides interglomerular contrast enhancement that is proportional to the magnitude of ON input to each glomerulus. This renewal application builds on achievements of the previous award and uses novel approaches to clarify the organization and functions of the neural network that initiates the computation of odors.