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.

这项研究的远距离目标是了解细胞在学习过程中建立关联的机制以及然后，神经元功能会改变。海洋蜗牛腹泻提供了一个有利的模型系统，用于分析简单的学习形式因为它的神经系统由相对较少的神经元组成，所以大而独特的可识别。防御的经典条件 Aplysia的提取反射类似于脊椎动物中的条件尊重数量。该系统中的调节研究证明在刺激或事件之间的学习关系中由单个神经细胞中的分子检测到。协会神经可塑性的形式，相关活性依赖性突触促进，发生在调节的感觉神经元内刺激途径，并有助于由调理。在这些感觉神经元中，在联想促进期间，调节的酶，钙/钙调蛋白敏感的腺苷环酶提供了联想刺激收敛的分子位点。钙感觉神经元活性期间的涌入提供了细胞条件刺激的表示；调节发射器提供代表无条件刺激的细胞信号。这细胞内信使循环放大器，由adenylyl合成循环酶参与触发加强的过程感觉神经元的突触连接。激活adenylyl 当短暂接触调制发射器时，循环酶会增强发射器紧接钙的增加。此外，当钙和调节发射器配对时，循环酶显示出与之相似的序列偏好，并且可能是基础的序列偏好条件刺激的调节序列偏好在训练过程中无条件的刺激之前。一个目的研究是分析负责此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在非社交和协会学习。细胞内使者的作用，包括循环放大器，将探索启动神经元变化。这由于离子电流调节而引起的神经元变化的重要性将被调查，包括动作电位变化和提高周围引发的感觉的可靠性信号在感觉神经元轴突中传播到中央突触终端。这些研究对于理解恢复过程可能很重要外围伤害以及学习的基本机制。