Mechanisms of interneurons in the olfactory bulb

嗅球中间神经元的机制

• 批准号: 7022292
• 负责人: NATHAN Eric SCHOPPA
• 金额: $ 31.27万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7022292
• 关键词: cell biology; cell component structure /function; charge coupled device camera; computer program /software; computer simulation; electrophysiology; granule cell; interneurons; laboratory rat; neurophysiology; olfactory lobe; phase contrast microscopy; sensory signal detection; video microscopy; voltage /patch clamp

The overall goal of this proposal is to understand the functional mechanisms of inhibitory interneurons in the mammalian olfactory bulb. These interneurons, called granule cells and periglomerular (PG) cells, are often proposed to impact olfactory information processing in one of two ways, either by synchronizing the activity of the bulb's output neurons (mitral cells) or by mediating lateral inhibitory interactions between mitral cells. However, the functional mechanisms of the interneurons are not well-understood. Studies in the first two Specific Aims of this proposal use patch-clamp recordings from interneurons in olfactory bulb slices in order to evaluate two mechanistic aspects of interneurons that we predict are critical for function. These include the mechanisms of synaptic activation of interneurons by mitral cells (Aim 1) and mechanisms that couple the activity of different interneurons (Aim 2). In Specific Aim 3, recordings from pairs of mitral cells in slices will be made to test the functional role of interneurons in synchronizing action potential-firing in mitral cells. A key novel aspect of our studies is our electrical stimulation paradigm. While previous studies have examined interneuron mechanisms under static conditions, we examine their functional properties under dynamic, more physiological conditions produced by low frequency stimulation of afferent olfactory nerve (ON) fibers. The results of our studies will lead to a direct understanding of how synchronized activity is generated in the bulb, and also point toward possible mechanisms that could alter such activity following olfactory learning or during pathological conditions, such as Alzheimer's and Parkinson's disease. In addition, our mechanistic studies of synchronized activity could provide insight into mechanisms of epileptogenic dysfunction in other brain circuits.

该提案的总体目标是了解哺乳动物嗅球中抑制性中间神经元的功能机制。这些中间神经元，称为颗粒细胞和肾小球周围（PG）细胞，通常被认为以两种方式之一影响嗅觉信息处理，要么通过同步球输出神经元（二尖瓣细胞）的活动，要么通过介导二尖瓣细胞之间的横向抑制相互作用。然而，中间神经元的功能机制尚不清楚。该提案的前两个具体目标的研究使用嗅球切片中中间神经元的膜片钳记录，以评估我们预测对功能至关重要的中间神经元的两个机制方面。其中包括二尖瓣细胞突触激活中间神经元的机制（目标 1）以及耦合不同中间神经元活动的机制（目标 2）。在具体目标 3 中，将对切片中的成对二尖瓣细胞进行记录，以测试中间神经元在同步二尖瓣细胞动作电位放电中的功能作用。我们研究的一个关键的新颖方面是我们的电刺激范例。虽然之前的研究是在静态条件下检查中间神经元机制，但我们在动态、更生理的条件下检查它们的功能特性，这些条件是由传入嗅神经（ON）纤维的低频刺激产生的。我们的研究结果将导致人们直接了解灯泡中如何产生同步活动，并指出在嗅觉学习后或在阿尔茨海默病和帕金森病等病理条件下改变此类活动的可能机制。此外，我们对同步活动的机制研究可以深入了解其他脑回路中致癫痫功能障碍的机制。