MECHANISMS OF PERSISTENT NEURAL ACTIVITY

持续神经活动的机制

• 批准号: 6195362
• 负责人: Hyunjune SEBASTIAN SEUNG
• 金额: $ 29.94万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6195362
• 关键词: behavioral /social science research tag; brain electrical activity; computational neuroscience; eye movements; goldfish; neural conduction; neural information processing; neural inhibition; neuronal transport; rhombencephalon; short term memory; synapses; voltage /patch clamp

The long-range goal of this research is to identify the cellular and circuit mechanisms responsible for maintaining persistent neural activity: a sustained change in sodium action potential firing related to short-term memory that has been observed in many brain areas. Our program combines experimental and theoretical studies of the oculomotor integrator, where persistent neural activity is related to a short-term memory of the current eye position. The experimental preparation is the goldfish, which, is particularly advantageous for a cellular and computational analysis of mechanisms. Our specific aims are to test the following hypotheses: 1. Storage of the memory of eye position is completely localized in hindbrain Area I. 2. Cellular mechanisms maintain persistent neural activity. 3. Circuit mechanisms maintain persistent neural activity. 4. The variability and synchrony of persistent neural activity reflects network interactions. Methods Persistent neural activity in awake goldfish will be measured and perturbed by intracellular recording to test hypothetical cellular mechanisms of persistent neural activity. The intrinsic and synaptic conductances of integrator neurons will be studied in vitro, and a numerical model will be constructed from the results. Synaptic connectivity will be determined by intracellular fills in vivo and dual recording in vitro, and incorporated into a network of conductance-based model neurons. The effects of pharmacological agents on behavior and neural activity will be compared with model predictions. The properties of correlated neural activity will be measured with multielectrode recordings, and compared with network models. Health relatedness Persistent neural activity has consistently been observed in brain areas important in short-term memory, a central component of many cognitive abilities. Some mental disorders, such as schizophrenia, may involve deficits in short- term memory.

这项研究的长期目标是确定负责维持持续神经活动的细胞和回路机制：在许多大脑区域中观察到的与短期记忆相关的钠动作电位放电的持续变化。我们的项目结合了动眼神经积分器的实验和理论研究，其中持续的神经活动与当前眼睛位置的短期记忆有关。 实验准备物是金鱼，它对于机制的细胞和计算分析特别有利。 我们的具体目标是测试以下假设： 1. 眼睛位置记忆的存储完全位于后脑 I 区。 2. 细胞机制维持持续的神经活动。 3. 回路机制维持持续的神经活动。 4.持续性神经活动的可变性和同步性反映了网络相互作用。方法 通过细胞内记录测量和扰乱清醒金鱼的持续神经活动，以测试持续神经活动的假设细胞机制。将在体外研究积分神经元的固有电导和突触电导，并根据结果构建数值模型。 突触连接将通过体内细胞内填充和体外双重记录来确定，并纳入基于电导的模型神经元网络中。 药物对行为和神经活动的影响将与模型预测进行比较。 相关神经活动的特性将通过多电极记录进行测量，并与网络模型进行比较。健康相关性 在短期记忆中重要的大脑区域中一直观察到持续的神经活动，短期记忆是许多认知能力的核心组成部分。 一些精神障碍，例如精神分裂症，可能涉及短期记忆缺陷。