NONASSOCIATIVE AND ASSOCIATIVE NEUROPLASTICITY

非联想和联想神经可塑性

基本信息

批准号：
2416179
负责人：
Thomas W Abrams
金额：
$ 23.72万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-09-30 至 1999-04-30
项目状态：
已结题

项目摘要

The long range goal of this research is to understand the cellular mechanisms by which associations are made during learning and by which neuronaI function is then altered. The marine snail Aplysia has provided an advantageous model system for the analysis of simple forms of learning because its nervous system consists of relatively few neurons, which are large and uniquely identifiable. Classical conditioning of the defensive withdrawal reflex of Aplysia resembles conditioning in vertebrates in a number of respects. Studies of conditioning in this system have demonstrated that during learning relationships between stimuli or events are detected by molecules within individual nerve cells. An associative form of neural plasticity, associative activity-dependent synaptic facilitation, occurs within the sensory neurons of the conditioning stimulus pathway, and contributes to the behavioral changes produced by conditioning. Within these sensory neurons, during associative facilitation, a dually- regulated enzyme, the calcium/calmodulin-sensitive adenylyl cyclase provides a molecular site of associative stimulus convergence. Calcium influx during a sensory neuron's activity provides a cellular representation of the conditioned stimulus; modulatory transmitter provides a cellular signal representing the unconditioned stimulus. The intracellular messenger cyclic AMP, which is synthesized by adenylyl cyclase participates in triggering the processes that strengthen the synaptic connections from the sensory neurons. Activation of the adenylyl cyclase by a brief exposure to modulatory transmitter is enhanced when the transmitter is immediately preceded by a increase in calcium. Furthermore, when calcium and modulatory transmitter are paired, the cyclase displays a sequence preference that parallels, and may underlie, the sequence preference of conditioning that the conditioned stimulus precede the unconditioned stimulus during training. One aim of this research is to analyze the molecular mechanisms responsible for this associative neural integration. This research will also investigate the mechanisms by which signaling from the sensory neurons is enhanced during both nonassociative and associative learning. The roles of intracellular messengers, including cyclic AMP, in initiating neuronal changes will be explored. The importance of neuronal changes due to modulation of ionic currents will be investigated, including a change in action potential shape and an increase in the reliability with which peripherally initiated sensory signals propagate in sensory neuron axons to central synaptic terminals. These studies may be important in understanding processes of recovery after peripheral injury, as well as basic mechanisms of learning.

这项研究的长期目标是了解细胞学习过程中建立关联的机制以及然后神经元功能发生改变。海洋蜗牛Aplysia 提供了用于分析简单学习形式的有利模型系统因为它的神经系统由相对较少的神经元组成，大且可唯一识别。防守的经典调理海兔的退缩反射类似于脊椎动物的条件反射尊重的数量。对该系统条件作用的研究证明在学习过程中刺激或事件之间的关系由单个神经细胞内的分子检测。一个联想神经可塑性的形式，关联活动依赖的突触促进，发生在条件反射的感觉神经元内刺激途径，并有助于产生的行为变化调理。在这些感觉神经元内，在联想促进过程中，双重- 调节酶，钙/钙调蛋白敏感的腺苷酸环化酶提供了联想刺激汇聚的分子位点。钙感觉神经元活动期间的流入提供了细胞条件刺激的表征；调制发射机提供代表无条件刺激的细胞信号。这细胞内信使环AMP，由腺苷酸合成环化酶参与触发加强来自感觉神经元的突触连接。腺苷酸的激活环化酶通过短暂暴露于调制发射器而增强发射器之前立即出现钙的增加。此外，当钙和调制发射器配对时，环化酶显示出平行的序列偏好，并且可能是其基础，条件刺激的顺序偏好在训练期间先于无条件刺激。这样做的目的之一研究的目的是分析造成这种情况的分子机制联想神经整合。这项研究还将调查信号传导的机制感觉神经元在非联想和联想期间都会增强联想学习。细胞内信使的作用包括将探讨环状 AMP 在引发神经元变化中的作用。这由于离子电流的调制而引起的神经元变化的重要性将进行研究，包括动作电位形状的变化和增加外周发起的感觉的可靠性信号在感觉神经元轴突中传播到中枢突触末端。这些研究对于理解恢复过程可能很重要外周损伤后，以及学习的基本机制。