DENDRITIC SIGNALING IN THE OLFACTORY BULB

描述（由申请人提供）：气味信息通过嗅觉受体的选择性激活进行编码，并在地形上映射到嗅球中的肾小球。我们广泛而长期的目标是了解球茎中的树突和突触信号机制，这些机制将这种映射的输入转化为输出神经元（二尖瓣细胞和簇状细胞）中气味编码的尖峰模式。我们将重点放在簇状细胞上，这是嗅球中主要神经元的一个主要类别，通常被忽略了。簇状细胞与二尖瓣细胞的不同之处在于它们的皮层突起、树突场、尖峰频率和分子接受范围的横向抑制调谐。我们的工作假设是，嗅球的感觉处理被包含簇状细胞和二尖瓣细胞的子回路分成平行的通路。我们将通过分析和对比簇状细胞相对于二尖瓣细胞的尖峰时间和同步，通过绘制连接簇状细胞和二尖瓣细胞的局部神经元中间回路的空间结构，以及通过确定尖峰同步的生物物理和突触机制来验证这一理论。我们还将分析簇状细胞到颗粒细胞连接镜像对称肾小球图的球内投射，并测试神经肽胆囊细胞分裂素在这些投射中作为共递质或调节剂的作用的特定模型。我们的工作将对调节感觉系统中节律性尖峰活动的差异编码和动态抑制机制产生新的见解。我们的实验方法包括在啮齿动物模型的切片准备中结合膜片钳电生理学和光学记录或刺激。这项工作解决了我们对处理感觉信息的嗅球回路的连通性和突触生理学知识的主要空白。这对于理解脑回路的同步性和动态性具有广泛的意义。这与提高我们对神经网络协调病理的理解有关，比如癫痫和痴呆。我们还在开发一种新的细胞模型方面迈出了开创性的一步，用于分析参与肿瘤发生的肽信号转导途径。

DESCRIPTION (provided by applicant): Odor information is encoded by selective activation of olfactory receptors and mapped topographically to glomeruli in the olfactory bulb. Our broad, long term objective is to understand dendritic and synaptic signaling mechanisms in the bulb that transform this mapped input into odor-encoding spike patterns in output neurons - the mitral cells and tufted cells. We focus on the tufted cells, a major class of principal neurons in the olfactory bulb that has been mostly ignored. Tufted cells differ from mitral cells in their cortical projections, dendritic fields, spike frequencies, and lateral inhibitory tuning of molecular receptive ranges. Our working hypothesis is that sensory processing in the olfactory bulb is split into parallel pathways by sub-circuits containing the tufted cells and mitral cells. We will test this theory by analyzing and contrasting the spike timing and synchronization of tufted cells relative to mitral cells, by mapping out the spatial structure of local interneuron circuits that link to tufted cells and mitral cells, and by determining biophysical and synaptic mechanisms of spike synchrony. We will also analyze the intrabulbar projections of tufted cells to granule cells linking mirror symmetric glomerular maps, and test a specific model for the role of the neuropeptide cholecytokinin as a co-transmitter or modulator in these projections. Our work will yield new insights into differential coding and dynamic inhibitory mechanisms regulating rhythmic spike activity in a sensory system. Our experimental approaches include a combination of patch-clamp electrophysiology and optical recording or stimulation in slice preparations in a rodent model. PUBLIC HEALTH RELEVANCE This work address a major gap in our knowledge of connectivity and synaptic physiology of circuits in the olfactory bulb that process sensory information. It has broad significance for understanding the synchronization and dynamics of brain circuits,.and is relevant to improving our understanding of pathologies in the coordination of neuronal networks, such as epilepsy and dementia. We also take pioneering steps in developing a new cellular model for analyzing a peptide signal transduction pathway that is involved in oncogenesis.