PLASTICITY OF INTRINSIC AND SYNAPTIC PROPERTIES OF CULTU

人们普遍认为，学习和记忆的能力是在 通过对神经系统的特性进行活动依赖性的修改， 行为背后的回路神经回路的输出取决于 突触连接和内在放电特性之间的相互作用 但尽管这些内在的重要性， 电路功能的神经元特性， 学习几乎只强调突触的作用， 修改.我们已经证明，孤立的龙虾口胃神经节 培养的神经元经历紧张性和紧张性之间的活动依赖性转换， 以钙依赖的方式激活和猝发激活状态。这些 转换是通过调节离子的表达产生的， 电导率这些研究表明， 像突触强度一样，可以通过 一个神经元的放电特性是神经元活动的一部分， 最近的激活历史的功能。 本建议将根据这些调查结果， 电生理和钙成像技术来解决 活动改变内在神经元放电的机制 特性.细胞内钙、蛋白质合成和 蛋白激酶在这一过程中将得到解决。我们将确定 单个神经突的局部激活是否可以局部改变 电导的大小或分布，以及这种修改是否 作用于对抗或加强突触输入。的长期目标 这个建议是为了了解内在的神经元特性， 突触强度被联合调节以编码经验。为了 为了研究内在可塑性和突触可塑性之间的相互作用， 已经开始发展一种皮层培养系统， 特定神经元群体的特性和突触特性可以 被研究，自发突触活动高。的 K02基金会给我提供的额外研究时间将 请允许我集中我个人的力量来发展这种新的文化 系统我相信这个系统将提供有关 学习和记忆的基石，以及经验在 决定和改变神经系统的结构和功能。

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.