SYNAPTIC PLASTICITY IN HIPPOCAMPAL MOSSY CELLS

齿状苔藓细胞是一种相对罕见的神经元群体， 非常容易受到过度兴奋性 输入. 虽然负责这一过程的细胞机制 漏洞是未知的，一个潜在的解释在于， 苔藓细胞调节自身强度的能力 突触输入 我观察到，在短暂的 细胞内注射去极化电流脉冲，有一个 自发兴奋性神经元的显著和持续增强 突触后电位（EPSP）记录在同一个细胞。 我 假设这种现象，去极化相关的增强， 可能会导致苔藓细胞的脆弱性 积极反馈途径：相对短暂的 去极化，例如当几个自发EPSP 重叠，可能会参与这一机制-加强后续的EPSP， 产生失控去极化和细胞死亡的可能性。 这种类型的进行性去极化，由大振幅 在颞叶癫痫的体外模型中观察到EPSPs 苔藓细胞选择性的脆弱 中的实验 在该提议中概述的大鼠海马切片被设计成 揭示这种可塑性的机制。 我们专注 第一，关于颗粒细胞/苔藓细胞的可塑性机制 突触，因为我的初步数据表明，大部分的DRP可能是 解释了这一点 通过检查 在诱导DRP之前和之后，我们希望确定 突触前或突触后部位是否受DRP调节， DRP是否代表一种跨突触可塑性。 初步实验表明，DRP与 短期增强（STP）在海马研究，我们预计 这里提出的实验将导致对 突触增强的一般原理。 可能发挥的作用 在DRP诱导过程中，苔藓细胞中的钙积累将 可以使用钙螯合剂和钙敏感荧光 染料Fura-2。 然后，我们将研究对增强的贡献 其他齿状和海马神经元的尖峰信号， 使用双重记录和切片与苔藓细胞突触耦合 其中海马和/或齿状回的亚区已经被 删除. 我预计这些研究将确定是否有一种形式的 “自我增强”是导致肺门兴奋性毒性损伤的主要原因 神经元，并可能导致新的见解的病因， 颞叶癫痫

Dentate mossy cells are a relatively rare population of neurons that are extremely vulnerable to excitotoxic damage from excess excitatory input. While the cellular mechanisms responsible for this vulnerability are not known, one potential explanation lies in the unusual ability of mossy cells to modulate the strength of their own synaptic inputs. I observed that following short periods of intracellularly-injected depolarizing current pulses, there was a dramatic and prolonged enhancement of spontaneous excitatory postsynaptic potentials (EPSPs) recorded in that same cell. I hypothesized that this phenomenon, depolarization-related potentiation, may contribute to the vulnerability of the mossy cells by generating a positive feedback pathway: relatively brief periods of depolarization, such as experienced when several spontaneous EPSPs overlap, may engage this mechanism--potentiating subsequent EPSPs and creating the potential for a runaway depolarization and cell death. This type of progressive depolarization, initiated by large amplitude EPSPs, has been observed in an in vitro model of temporal lobe epilepsy in which mossy cells are selectively vulnerable. The experiments in rat hippocampal slices outlined in this proposal are designed to uncover the mechanisms that underlie this form of plasticity. We focus first on the mechanisms of plasticity at the granule cell/mossy cell synapse since my preliminary data suggests that much of DRP could be explained by modulation of this synapse. By examining properties of miniature EPSCs before and after induction of DRP, we hope to ascertain whether the pre- or postsynaptic site is modulated by DRP, and thus whether DRP represents a form of trans-synaptic plasticity. Preliminary experiments suggest that DRP shares many similarities with short-term potentiation (STP) studied in the hippocampus; we anticipate that the experiments proposed here will lead to new understanding of general principles of synaptic potentiation. The potential role calcium accumulation in the mossy cells in the induction of DRP will be tested using calcium chelators and the calcium-sensitive fluorescent dye, fura-2. We then will examine the contribution to the potentiation from spiking in other dentate and hippocampal neurons which are synaptically coupled to mossy cells using dual recordings and slices in which subfields of the hippocampus and/or dentate gyrus have been removed. I anticipate that these studies will determine if a form of "self-potentiation" is responsible for the excitotoxic damage to hilar neurons in vitro and may lead to new insights into the etiology of hippocampal-onset temporal lobe epilepsy.