Mechanisms of interneurons in the olfactory bulb

嗅球中间神经元的机制

• 批准号: 7383813
• 负责人: NATHAN Eric SCHOPPA
• 金额: $ 31.69万
• 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/7383813
• 关键词: AMPA Receptors; Action Potentials; Alzheimer' s Disease; Brain; Cells; Class; Computer information processing; Condition; Coupling; Data; Electric Stimulation; Epilepsy; Fire - disasters; Foundations; Frequencies; Functional disorder; Goals; Interneuron function; Interneurons; Lateral; Lead; Location; Measurement; Mediating; Methods; Morus; N-Methyl-D-Aspartate Receptors; Nerve Fibers; Neurons; Neurotransmitters; Odorant Receptors; Olfactory Learning; Olfactory Nerve; Output; Parkinson Disease; Pattern; Physiological; Property; Rattus; Research Personnel; Role; Sensory; Signal Transduction; Slice; Stimulus; Synapses; Synaptic Potentials; Testing; Time; Whole-Cell Recordings; gamma-Aminobutyric Acid; granule cell; in vivo; insight; novel; olfactory bulb; patch clamp; programs; research study; response

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.

本研究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，称为颗粒细胞和小球周围细胞（PG），通常被认为以两种方式之一影响嗅觉信息处理，要么通过同步球茎输出神经元（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。本提案的前两个特定目标的研究使用了嗅球切片中中间神经元的膜片钳记录，以评估我们预测的对功能至关重要的中间神经元的两个机制方面。这些包括二尖瓣细胞对中间神经元的突触激活机制（目的1）和不同中间神经元活性的偶联机制（目的2）。在特异性目标3中，将对二尖瓣细胞切片进行记录，以测试中间神经元在二尖瓣细胞同步动作电位放电中的功能作用。我们研究的一个关键新颖方面是我们的电刺激范式。虽然之前的研究已经在静态条件下研究了中间神经元的机制，但我们在低频刺激传入嗅神经纤维产生的动态、更生理的条件下研究了它们的功能特性。我们的研究结果将导致对球茎中同步活动如何产生的直接理解，并指出可能的机制，可以在嗅觉学习或病理条件下改变这种活动，如阿尔茨海默氏症和帕金森病。此外，我们对同步活动的机制研究可以为其他脑回路中致癫痫功能障碍的机制提供见解。