Neuronal Specialization and Diversity

神经元的专业化和多样性

• 批准号: 9876032
• 负责人: Nelson Spruston
• 金额: $ 44.01万
• 依托单位: Northwestern University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-15 至 2005-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9876032&HistoricalAwards=false
• 关键词: Neuronal; Specialization; Diversity

Nelson SprustonIBN-9876032The central nervous system (CNS) is made up of approximately 100 billion nerve cells. Most of these neurons communicate with one another at contact points called synapses. On one side of the synapse, the speaker (the presynaptic neuron) communicates via action potentials - electrical signals about 100 mV in amplitude and 1-2 ms in duration. On the other side, the listener (the postsynaptic neuron) interprets these signals arriving simultaneously from thousands of presynaptic neurons. This conversation is complicated by the fact that not all neurons speak the same language. Some neurons fire as few as a few action potentials per second; others fire as many as a thousand action potentials per second. Differences are also observed in the patterns of action potential firing. The biological underpinnings of action potential firing patterns are largely determined by pore-forming molecules called ion channels. A new avenue of research into the mechanisms responsible for variations in action potential firing patterns is to study the properties of ion channels located in different parts of the neuron. For example the axon, which generally forms the presynaptic side of the synapse, expresses different ion channels than the dendrites, which forms the postsynaptic side of the synapse. Here I propose to use new technology to study the properties of ion channels in the dendrites of neurons in an area of the brain called subiculum. This area is part of the hippocampus, which is involved in learning and memory. Neurons in the subiculum are known to generate clusters of action potentials called bursts. This pattern is very different than that of their nearest neighbors in the CA1 region of the hippocampus, which are morphologically similar, but cannot generate bursts of action potentials. I propose to perform experiments that will test the hypothesis that the bursting observed in subicular neurons is caused by specialized properties of sodium and/or potassium channels in the dendrites of these neurons. Using recently developed technology, the properties of channels in the dendrites of subicular neurons will be compared to those in CA1 neurons determined in previous and ongoing studies in my lab. Together with action potential recordings from dendrites, pharmacological manipulations, and computer modeling studies, I aim to elucidate the differences between subicular and CA1 neurons that are responsible for the very different action potential firing patterns in these two cell types. The proposal also contains an educational component designed to teach undergraduate students about the importance of neuronal specialization in the central nervous system, and thebiological mechanisms underlying neuronal diversity.

纳尔逊SprustonIBN-9876032中枢神经系统（CNS）由大约1000亿个神经细胞组成。大多数神经元在称为突触的接触点上相互交流。在突触的一侧，说话者（突触前神经元）通过动作电位进行交流，动作电位是一种幅度约为100 mV、持续时间约为1-2 ms的电信号。另一方面，听者（突触后神经元）解释这些同时来自数千个突触前神经元的信号。这个对话是复杂的，因为不是所有的神经元都说同一种语言。有些神经元每秒只发出几个动作电位，而有些神经元每秒发出多达一千个动作电位。 在动作电位放电模式中也观察到差异。 动作电位放电模式的生物学基础在很大程度上是由称为离子通道的成孔分子决定的。一个新的研究方向是研究位于神经元不同部位的离子通道的特性，这是研究动作电位放电模式变化机制的一个新途径。例如，通常形成突触的突触前侧的轴突表达与形成突触的突触后侧的树突不同的离子通道。在这里，我建议使用新的技术来研究离子通道在神经元的树突在大脑的一个区域称为下托的属性。这个区域是海马体的一部分，海马体与学习和记忆有关。已知下托中的神经元产生称为爆发的动作电位簇。这种模式与海马CA 1区的最近邻居非常不同，它们在形态上相似，但不能产生动作电位的爆发。 我建议进行实验，将测试的假设，即观察到的下托神经元的爆裂是由这些神经元的树突中的钠和/或钾通道的专门属性。使用最近开发的技术，下托神经元树突中的通道特性将与我实验室先前和正在进行的研究中确定的CA 1神经元中的通道特性进行比较。再加上动作电位记录树突，药理学操作，计算机建模研究，我的目标是阐明下托和CA 1神经元，负责非常不同的动作电位放电模式，在这两种细胞类型之间的差异。该提案还包含一个教育部分，旨在向本科生讲授中枢神经系统神经元专业化的重要性，以及神经元多样性背后的生物学机制。