Cyclic nucleotide modulation of olfactory sensory input

描述(申请人提供)：嗅觉对人类生活有很大贡献。气味提示强烈的特定于环境的记忆，并在一个人的感知和对愉快和有害刺激做出反应的能力中发挥重要作用。嗅觉感受器神经元树突状纤毛中的环核苷酸门控通道(CNGC)是感觉传导过程中的重要组成部分。在Orns的轴突和突触终末表达的CNGC的作用还不是很清楚。 本研究的主要目的是研究环核苷酸和CNGC对嗅球神经元和突触传递的调节作用。为了做到这一点，从嗅神经接受突触输入的神经元将被整个细胞膜片钳住。第一个目的是确定增加细胞内环核苷酸浓度是否以CNGC依赖的方式调节嗅神经介导的突触传递。接下来，我们将研究CNGC激活调节神经递质释放的确切机制。最终的具体目标是确定鳞茎中有助于CNGC依赖的调节的内源性信号机制。这些实验将提供一个更完整的了解CNGC如何在嗅觉加工中发挥作用。此外，拟议的研究将有助于解决CNGC依赖信号的缺陷如何导致嗅觉处理错误。

DESCRIPTION (provided by applicant): The sense of smell contributes significantly to human life. Odors cue strong context-specific memories and play an important role in one's ability to sense and respond to both pleasant and noxious stimuli. Cyclic nucleotide-gated channels (CNGCs) in the dendritic cilia of olfactory receptor neurons (ORNs) are a critical component of the process by which sensory transduction occurs. The role of CNGCs expressed in the axons and synaptic terminals of ORNs is much less clear. The primary objective of this proposal is to examine modulation of synaptic transmission between ORNs and neurons in the olfactory bulb by cyclic nucleotides and CNGCs. To do this, neurons that receive synaptic input from the olfactory nerve will be whole cell patch clamped. The first aim is to determine whether raising the intracellular concentration of cyclic nucleotides modulates olfactory nerve-mediated synaptic transmission in a CNGC-dependent manner. Next the precise mechanism by which activation of CNGCs regulates neurotransmitter release will be examined. The final specific aim seeks to identify endogenous signaling mechanisms in the bulb that contribute to CNGC-dependent modulation. These experiments will provide a more complete understanding of how CNGCs contribute to olfactory processing. Moreover, the proposed research will help address how deficits in CNGC-dependent signaling lead to olfactory processing errors.