CELLULAR MECHANISMS AND FUNCTIONAL CONTRIBUTION BI-DIRECTIONAL SYNAPTIC PLASTICI

细胞机制和功能贡献双向突触塑料

• 批准号: 7381103
• 负责人: Brian Donald Burrell
• 金额: $ 12.01万
• 依托单位: UNIVERSITY OF SOUTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381103
• 关键词: CELLULAR; MECHANISMS; FUNCTIONAL; CONTRIBUTION; BI

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Learning is perhaps the most malleable form of adaptive behavior and activity-dependent changes in synaptic transmission, such as long-term potentiation (LTP) or long-term depression (LTD), are thought to play a critical role in learning and subsequent memory formation. An emerging issue in the study of activity-dependent synaptic plasticity and its contribution to learning has been the realization that changes initiated at one synapse can spread to other inactive synapses. The induction of LTP at one set of synapses that simultaneously leads to LTD in surrounding inputs to a shared postsynaptic neuron is one example that has been observed in synapses in the hippocampus, visual cortex and amygdala. How this homosynaptic LTP and heterosynaptic LTD are generated, how they interact and their functional relevance is crucial to understanding the cellular basis of learning in particular and adaptive behavior in general. In the leech CNS, induction of LTP in synaptic connections between touch mechanoreceptive neurons (T-cells) and the S-cell (an interneuron known to be critical for some forms of learning of the defensive shortening reflex) also produces LTD in synapses made by non-tetanized T-cells onto the same postsynaptic S-cell. Homosynaptic LTP (homLTP) at T-S synapses is NMDA receptor independent while heterosynaptic LTD is NMDA receptor dependent (Burrell & Sahley, 2004). One possible function of this pattern of plasticity is to "tune" afferent input to a postsynaptic cell leading to improved stimulus specificity. Using the leech model system we propose to examine the cellular mechanisms that mediate homLTP and hetLTD. Furthermore, we will examine how induction of homLTP/hetLTD affects the functional output (in terms of number of action potentials) of the S-cell in response to touch cell input initiated at the skin. Finally, we will determine whether homLTP/hetLTD contributes to stimulus specificity between learned and neutral stimuli during associative learning of the shortening reflex. This project adheres to the Center?s theme of Neural Mechanisms of Adaptive Behavior in that the proposed experiments span from studies of cellular processes mediating neuroplasticity to the effects of such plasticity on learning at the behavioral level.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。学习可能是适应性行为中最具可塑性的形式，突触传递中的活动依赖性变化，例如长时程增强（LTP）或长期抑制（LTD），被认为在学习和随后的记忆形成中发挥着关键作用。活动依赖性突触可塑性及其对学习的贡献研究中的一个新问题是认识到在一个突触引发的变化可以传播到其他不活动的突触。在一组突触处诱导 LTP，同时导致周围共享突触后神经元的输入产生 LTD，这是在海马体、视觉皮层和杏仁核的突触中观察到的一个例子。同突触 LTP 和异突触 LTD 是如何产生的、它们如何相互作用以及它们的功能相关性对于理解特定学习和一般适应性行为的细胞基础至关重要。在水蛭中枢神经系统中，触摸机械感受神经元（T 细胞）和 S 细胞（一种已知对某些形式的防御性缩短反射的学习至关重要的中间神经元）之间的突触连接中 LTP 的诱导，也会在由非破伤风 T 细胞与同一突触后 S 细胞形成的突触中产生 LTD。 T-S 突触的同质突触 LTP (homLTP) 不依赖于 NMDA 受体，而异质突触 LTD 则依赖于 NMDA 受体 (Burrell & Sahley, 2004)。这种可塑性模式的一个可能的功能是“调整”突触后细胞的传入输入，从而提高刺激特异性。我们建议使用水蛭模型系统来检查介导 homLTP 和 hetLTD 的细胞机制。此外，我们将研究 homLTP/hetLTD 的诱导如何影响 S 细胞响应皮肤启动的触摸细胞输入的功能输出（以动作电位的数量表示）。最后，我们将确定在缩短反射的联想学习过程中，homLTP/hetLTD 是否有助于习得刺激和中性刺激之间的刺激特异性。该项目遵循该中心的“适应性行为的神经机制”主题，因为拟议的实验涵盖介导神经可塑性的细胞过程的研究，以及这种可塑性对行为水平学习的影响。