Cyclic nucleotide modulation of olfactory sensory input

描述（由申请人提供）：嗅觉对人类生活有重要贡献。气味提示强烈的上下文特定的记忆，并在一个人的感知能力和对愉快和有害刺激的反应中发挥重要作用。嗅觉受体神经元（ORN）树突状纤毛中的环核苷酸门控通道（CNGC）是感觉传导过程的关键组成部分。CNGC在ORN的轴突和突触末梢中表达的作用还不太清楚。 这个建议的主要目的是检查调制的ORN和嗅球神经元之间的突触传递的环核苷酸和CNGC。为了做到这一点，从嗅觉神经接收突触输入的神经元将被全细胞膜片钳。第一个目的是确定是否提高细胞内浓度的环核苷酸调制嗅神经介导的突触传递CNGC依赖的方式。接下来将检查CNGC的激活调节神经递质释放的精确机制。最终的具体目标是确定球茎中有助于CNGC依赖性调节的内源信号机制。这些实验将提供一个更完整的了解CNGC如何有助于嗅觉加工。此外，拟议的研究将有助于解决CNGC依赖性信号传导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.