MECHANISMS OF PERSISTENT NEURAL ACTIVITY

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电路机制：在许多大脑区域观察到的与短期记忆相关的钠动作电位放电的持续变化。我们的程序结合了对动眼运动积分器的实验和理论研究，其中持续的神经活动与对当前眼睛位置的短期记忆有关。实验准备的是金鱼，这是特别有利的细胞和计算分析的机制。我们的具体目标是检验以下假设：1.眼睛位置记忆的存储完全局限于后脑区。2.细胞机制维持持续的神经活动。3.电路机制维持持续的神经活动。4.持续神经活动的变异性和同步性反映了网络的相互作用。方法用细胞内记录的方法测量和扰动清醒金鱼的持续神经活动，以检验持续神经活动的假想细胞机制。整合神经元的本征电导和突触电导将在体外进行研究，并将根据结果构建一个数值模型。突触连接将通过体内细胞内填充和体外双重记录来确定，并被整合到基于电导的模型神经元网络中。药理制剂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用多电极记录来测量，并与网络模型进行比较。与健康有关的持续性神经活动在大脑中对短期记忆很重要的区域一直被观察到，而短期记忆是许多认知能力的中心组成部分。一些精神障碍，如精神分裂症，可能与短期记忆缺陷有关。

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.