Neuronal Specialization and Diversity

Nelson SprustonIBN-9876032中枢神经系统由大约1000亿个神经细胞组成。这些神经元中的大多数在称为突触的接触点上相互通信。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--动作电位是幅度约为100 mV、持续时间为1-2ms的电信号。另一方面，听者(突触后神经元)解释这些信号，这些信号同时来自数千个突触前神经元。由于并非所有神经元都说同一种语言，这种对话变得复杂起来。有些神经元每秒只发出几个动作电位，另一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上也观察到了差异。动作电位放电模式的生物学基础在很大程度上由称为离子通道的孔洞形成分子决定。研究动作电位放电模式变化的机制的一个新途径是研究位于神经元不同部分的离子通道的特性。例如，轴突通常构成突触的突触前侧，它表达的离子通道与树突不同，树突构成突触的突触后侧。在这里，我提议使用新技术来研究大脑下丘脑区神经元树突中离子通道的特性。这一区域是海马体的一部分，海马体参与学习和记忆。众所周知，下丘脑中的神经元会产生一连串的动作电位，称为猝发。这种模式与它们在海马区CA1区的近邻模式非常不同，后者在形态上相似，但不能产生动作电位的爆发。我建议进行一些实验，以验证这样一种假设，即在下丘脑神经元中观察到的爆裂是由这些神经元树突中钠和/或钾通道的特殊性质引起的。利用最新开发的技术，我们将把亚束下神经元树突中的通道特性与我实验室以前和正在进行的研究中确定的CA1神经元中的通道特性进行比较。结合来自树突的动作电位记录、药理学操作和计算机模拟研究，我的目的是阐明亚束状核和CA1神经元之间的差异，这些差异是导致这两种细胞类型的动作电位放电模式截然不同的原因。该提案还包含一个教育部分，旨在向本科生传授神经元特化在中枢神经系统中的重要性，以及神经元多样性背后的生物机制。

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.