NONASSOCIATIVE AND ASSOCIATIVE NEUROPLASTICITY

非联想和联想神经可塑性

基本信息

批准号：
6625388
负责人：
Thomas W Abrams
金额：
$ 29.7万
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 2005-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6625388
关键词：
Aplysia afferent nerve association learning behavioral /social science research tag behavioral habituation /sensitization calcium flux conditioning enzyme activity gene induction /repression molecular psychobiology neural facilitation neural plasticity protein kinase reflex regulatory gene serotonin synapses touch

项目摘要

DESCRIPTION (Adapted from the Investigator's Abstract) The-long range goal of this program is to understand the cellular and molecular mechanisms by which experience and learning alter synaptic connections. The synaptic connections from the tactile sensory neurons that mediate the defensive withdrawal reflex of the marine snail Aplysia have provided a powerful, tractable and productive model system for the analysis of simple forms of learning and behavioral modification. We have recently identified a new form of synaptic plasticity, burst-dependent protection from synaptic depression, that allows these animals to remain attentive to stimuli that are important, but repetitive; these stimuli would otherwise be ignored due to habituation. Burst-dependent protection provides an effective switch that prevents the process of synaptic decrement that normally occurs when these neurons are repeatedly activated. Investigation of this mechanism revealed that synaptic decrement in these cells actually involves an active switching-off of individual synaptic sites rather than a "passive run-down" due to depletion of transmitter stores. These studies will analyze the cellular processes responsible for synaptic decrement and how this decrement is prevented through burst-dependent protection when a repetitive stimulus is more salient. The findings may be important for improving alertness and learning in non-novel environments, e.g. at work or in the classroom, and for maintaining synaptic function in clinical situations where synapses deteriorate. These sensory neuron synapses can also be strengthened through associative plasticity during classical conditioning that closely resembles conditioning in mammals. Our work has demonstrated that during this learning, relationships between stimuli or events are recognized by dually regulated proteins that function as molecular coincidence detectors. During conditioning, the enzyme adenylyl cyclase provides a molecular site of associative stimulus convergence that integrates two signals triggered by behavioral events: calcium influx and release of modulatory transmitter. We have found that a number of the integration properties of the adenylyl cyclase can account for characteristic features of the conditioning. When the adenylyl cyclase, which is also involved in learning in mammals, detects relationships between stimuli, it initiates strengthening of synaptic connections via the transient intracellular messenger cAMP. The formation of long-term memory involves the conversion of this transient signal to stable synaptic modifications, which is mediated by activation of immediate-early genes. Our molecular experiment will investigate how associated training with pairing of calcium influx and modulatory transmitter enhances induction of immediate-early genes.

描述（改编自调查员的摘要）该程序的长范围目标是了解细胞和分子经验和学习的机制改变了突触连接。这介导的触觉感觉神经元的突触连接海洋蜗牛腹泻的防御性撤回反射提供了功能强大，可拖延和富有成效的模型系统，用于分析简单学习和行为修改的形式。我们最近确定了一种新形式的突触可塑性，依赖于爆发防止突触抑郁症，使这些动物保持注意重要但重复的刺激；这些刺激会否则由于习惯而被忽略。爆发依赖的保护提供了有效的开关阻止了通常的突触减少过程当这些神经元反复激活时发生。对此进行调查机制表明，这些细胞的突触减少实际上涉及单个突触站点的主动关闭而不是“被动” 由于发射机存储的耗竭，破失的”。这些研究将分析负责突触减少的细胞过程以及如何当重复时，通过爆发依赖的保护阻止减少刺激更为显着。这些发现对于提高机敏可能很重要并在非小型环境中学习，例如在工作或教室里，用于在突触的临床情况下保持突触功能恶化。这些感觉神经元突触也可以通过联想来增强在经典条件期间的可塑性非常类似于条件哺乳动物。我们的工作表明，在学习期间，人际关系在刺激或事件之间，通过双重调节的蛋白质认识到充当分子巧合检测器。在调节期间，酶腺苷酸环化酶提供了缔合刺激收敛的分子位点集成了由行为事件触发的两个信号：钙涌入和释放调节发射器。我们发现许多腺苷酸环化酶的集成特性可以解释特征调理的特征。当同样涉及的腺苷酸环化酶在哺乳动物中学习，检测刺激之间的关系，它启动通过瞬时细胞内信使加强突触连接营。长期记忆的形成涉及转换瞬态信号到稳定的突触修饰，该修饰是由激活即时基因。我们的分子实验将研究与钙涌入和调节配对的相关训练如何发射器增强了立即诱导基因的诱导。