PLASTICITY OF INTRINSIC AND SYNAPTIC PROPERTIES OF CULTU

人们普遍认为，学习和记忆的能力是由 通过活动依赖的神经属性的改变 行为背后的环路。神经电路的输出取决于 突触连接与固有放电特性之间的相互作用 单个神经元，但尽管这些固有的 电路功能的神经元特性，对其机制的研究 学习几乎完全强调突触的作用 修改。我们已经证明，分离的龙虾口胃神经节 培养的神经元在紧张期和紧张期之间经历活动依赖的转换 以钙依赖的方式激发和爆发激发状态。这些 转变是通过调节离子的表达而产生的 导电性。这些研究表明，内在的激发特性 神经元的数量，就像突触的强度一样，可以通过 正在进行的活动，神经元的放电特性在A部分 其近期激活史的功能。 该提案将通过使用以下方式对这些调查结果进行跟进 电生理和钙成像技术解决 活动改变固有神经元放电的机制 属性。细胞内钙离子、蛋白质合成和 这一过程中的蛋白激酶将被解决。我们将决定 局部激活单个轴突是否可以局部改变 电导的大小或分布，以及这种修改是否 起到对抗或加强突触输入的作用。的长期目标是 这一建议是为了了解神经元的内在属性和 突触强度是共同调节的，以编码经验。按顺序 为了研究内在可塑性和突触可塑性之间的相互作用，我们 已经开始发展一种皮质培养系统，在这种系统中 特定神经元群体的属性和突触属性可以 被研究，并在自发突触活动较高的地方。这个 K02奖金将为我提供额外的研究时间 请允许我将个人精力集中在发展这种新文化上 系统。我相信这个系统将提供有关 学习和记忆的积木，以及经验在 确定和修改神经系统结构和功能。

It is generally accepted that the abilities to learn and remember arise through activity-dependent modifications in the properties of the neural circuits underlying behavior. The outputs of neural circuits depend on an interplay between synaptic connections and the intrinsic firing properties of individual neurons, but despite the importance of these intrinsic neuronal properties for circuit function, studies on the mechanisms of learning have stressed almost exclusively the role of synaptic modifications. We have shown that isolated lobster stomatogastric ganglion neurons in culture undergo activity-dependent transitions between tonic firing and burst firing states in a calcium-dependent manner. These transitions are produced by regulation of the expression of ionic conductances. These studies indicate that the intrinsic firing properties of neurons, like synaptic strengths, can be continuously modified by ongoing activity, and that the firing properties of a neuron are in part a function of its recent history of activation. This proposal will follow up on these findings by using electrophysiological and calcium imaging techniques to address the mechanisms by which activity modifies intrinsic neuronal firing properties. The role of intracellular calcium, protein synthesis, and protein kinases in this process will be addressed. We will determine whether local activation of individual neurites can locally modify the magnitude or distribution of conductances, and whether this modification acts to oppose or to potentiate synaptic inputs. The long-term goal of this proposal is to understand how intrinsic neuronal properties and synaptic strengths are conjointly regulated to encode experience. In order to study the interactions between intrinsic and synaptic plasticity, we have begun to develop a cortical culture system in which the firing properties and synaptic properties of specific populations of neurons can be studied, and where spontaneous synaptic activity is high. The additional time for research afforded me by the award of a K02 grant will allow me concentrate my personal effort on developing this new culture system. I believe this system will provide essential information about the building blocks of learning and memory, and the role of experience in determining and modifying nervous system structure and function.