The Functional Organization of Inhibition in the Olfactory Bulb In Vivo

描述（由申请人提供）：在嗅球中，单个突触将传入感觉输入和投射到高级皮质区域的主要神经元分开。然而，在这个结构中的绝大多数细胞和连接都致力于两个不同的抑制回路：一个位于肾小球层表面，一个涉及肾小球下层的颗粒细胞。在它们最初被描述后不久， 这些抑制回路可能以类似于其他初级感觉区域的方式提供中心-周围抑制。然而，这些回路在体内被嗅觉刺激激活的方式还有待证实，它们在塑造嗅球输出中的重要性仍然存在争议。在这个提议中，抑制从嗅觉受体神经元输入的位点通过肾小球层的横向传播将被直接可视化，以确定在这个水平上的侧抑制如何可能有助于嗅觉信息处理。此外，将在识别的嗅球输出神经元中评估来自两侧回路的抑制的突触后效应。这些实验将提供重要的见解，侧抑制电路在体内的作用，并通过确定不同类别的输出神经元的兴奋性thse电路的差异效应，更好地理解平行的路径投射到更高的大脑结构。 公共卫生相关性：动物的感觉环境在大脑中的表现是感觉区域神经元之间的特定连接模式的结果。为了更好地了解嗅觉系统，更普遍地说，所有的感觉系统，处理感觉信息，这个建议的目的是描述空间传播的活动抑制回路和它们的影响，在嗅球的输出神经元的行为时，活的动物与气味。本课程的研究将提供有关气味的信息通过嗅球中的局部回路转化的方式的新见解，以便我们可以更好地了解大脑如何处理动物外周产生的感觉信号，并更好地解决由损伤和疾病引起的感觉缺陷。

DESCRIPTION (provided by applicant): In the olfactory bulb, a single synapse separates afferent sensory input and the principal neurons that project to higher cortical areas. Nevertheless, the vast majority of cells and connections in this structure are devoted to two distinct inhibitory circuits: one located superficially in the glomerular layer and one involving granule cells in infraglomerular layers. Soon after they were initially described, it was suggested that these inhibitory circuits might provide center-surround inhibition in an analogous fashion to other primary sensory areas. Nevertheless, the manner in which these circuits are activated by olfactory stimuli in vivo has yet to be demonstrated, and their importance in shaping olfactory bulb output remains controversial. In this proposal, the spread of inhibition laterally from the sites of olfactory receptor neuron input through the glomerular layer will be directly visualized t determine how lateral inhibition at this level might contribute to olfactory information processing In addition, the postsynaptic effect of inhibition arising from both lateral circuits will be assesed in identified olfactory bulb output neurons. These experiments will provide crucial insights into the role of lateral inhibitory circuits in vivo, and, by determining the differential effects of thse circuits on the excitability of different classes of output neurons, a better understanding of parallel pathways projecting to higher brain structures. PUBLIC HEALTH RELEVANCE: The representation of an animal's sensory environment in the brain comes about as a result of specific patterns of connectivity between neurons in sensory areas. To better understand how the olfactory system, and, more generally, all sensory systems, process sensory information, this proposal aims to describe the spatial spread of activity in inhibitory circuits and their impact on output neuron behavior in the olfactory bulb when the live animal is presented with odors. This course of study will provide new insights into the ways that information about odors are transformed by local circuits in the olfactory bulb so that we may better understand how the brain processes sensory signals generated in the animal's periphery and better address sensory deficits caused by injury and disease with new therapeutic approaches.