Olfactory Glomeruli: Cellular and Network Mechanisms

描述(申请人提供)：肾小球是嗅觉通路中突触整合的初始位置。嗅神经(ON)轴突由表达相同气味感受器的嗅觉感受器神经元发出，投射到主嗅球内的一个或几个肾小球，在那里它们与二尖瓣/簇状细胞(MC/TCS)和局部球旁中间神经元(JG)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小部分刻板印象的神经元亚型组成的，这些亚型专门组织起来执行离散的网络操作。这些网络操作决定了从ON终端到MOB的输出神经元MC和TCS的传递函数。我们进一步假设，这些肾小球转移功能主要取决于每个肾小球中ON活性的大小。对整个肾小球整体的模式活动的分析发生在肾小球网络的下游。 目标1将确定JG神经元突触关系的递质和受体。AIMS 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将验证DA和GABA能JG细胞通过改变钙离子介导的递质释放而对终末产生突触前抑制的假说，以及(Ii)将在体内使用钙成像和气味刺激来检验突触前抑制作用以扩大肾小球输出的动态反应范围的假说。Aim 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丛生细胞的功能是放大和同步肾小球对气味刺激的输出反应。目的4验证短轴突JG细胞在调节局部肾小球侧向抑制中的作用。这种侧向抑制提供了肾小球间的对比增强，这与每个肾小球的ON输入的大小成正比。 这一续展申请建立在前一次奖项的成果基础上，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.