CELLULAR MECHANISMS AND FUNCTIONAL CONTRIBUTION BI-DIRECTIONAL SYNAPTIC PLASTICI

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 学习可能是最具可塑性的适应行为形式，突触传递中依赖活动的变化，如长时程增强(LTP)或长时抑制(LTD)，被认为在学习和随后的记忆形成中发挥关键作用。在研究活动依赖的突触可塑性及其对学习的贡献方面，一个新出现的问题是人们意识到在一个突触开始的变化可以传播到其他不活跃的突触。LTP在一组突触的诱导，同时导致LTP在周围输入到共享的突触后神经元中的LTD，这是在海马体、视觉皮质和杏仁核的突触中观察到的一个例子。这种同突触LTP和异突触LTD是如何产生的，它们是如何相互作用的，以及它们的功能相关性对于理解学习的细胞基础和一般的适应行为至关重要。在水蚤中枢神经系统中，在接触机械感受性神经元(T细胞)和S细胞(已知的中间神经元，对某些形式的防御性缩短反射的学习至关重要)之间的突触连接中诱导LTP，也在未强直的T细胞与相同的突触后S细胞之间的突触中产生LTD。位于T-S突触的同源突触LTP不依赖于N-甲基-D-天冬氨酸受体，而异向突触LTP则依赖N-甲基-D-天冬氨酸受体(Burrell&Sahley，2004)。这种可塑性模式的一个可能功能是“调整”到突触后细胞的传入输入，从而提高刺激特异性。利用Leech模型系统，我们建议研究调节人LTP和hetLTD的细胞机制。此外，我们将研究在皮肤启动的触觉细胞输入时，homLTP/hetLTD的诱导如何影响S细胞的功能输出(根据动作电位的数量)。最后，我们将确定在短缩反射的联想学习过程中，homLTP/hetLTD是否有助于获得性刺激和中性刺激之间的刺激特异性。该项目遵循S中心关于适应行为的神经机制的主题，因为拟议的实验涵盖了从调节神经可塑性的细胞过程的研究到这种可塑性在行为水平上对学习的影响的研究。

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.