Olfactory Glomeruli: Cellular and Network Mechanisms

描述（申请者提供）：肾小球是嗅觉通路突触整合的初始部位。来自嗅觉受体神经元的嗅觉神经轴突（ON）表达相同的气味受体，投射到主嗅球内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/TCs）的顶端树突和局部的肾小球旁（JG）中间神经元突触。因此，每个肾小球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由一组定型的神经元亚型组成，专门组织以执行离散的网络操作。这些网络操作决定了从ON终端到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取决于每个肾小球on活性的大小。在肾小球网络的下游对整个肾小球整体的模式活动进行分析。

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.