MODULATION OF SYNAPTIC EFFICACY & MECHANISMS OF EPILEPSY

这项研究的目的是了解生理机制， 海马体中的兴奋和抑制可以通过 基于激活的模式的相对短的时间段， 突触 我们的假设是， 兴奋性和抑制性突触功效是负责的，至少在 部分，对于相对稳定的发作间期活动和 缉获量和缉获活动从重点地区蔓延的情况 CNS正常区域的异常。 通过增加我们对 这些过程中，希望新的战略，预防或治疗 癫痫会发展。 这些实验将在一种新的制备的非常低的 大鼠海马神经元的密度分离培养物。 录音将 用单个神经元的全细胞膜片钳电极和 孤立的成对突触连接的神经元。 突触 神经元之间的相互作用也将进行组织学分析， 技术. 微型突触电位的性质，无论是微型- 将对EPSC和小型IPSC进行检查，并确定它们是否 就像量子假说所预测的那样。 mini-psc的变化 振幅、形状或频率将用于帮助确定频率 突触效能的依赖性变化是由于突触前或突触后的神经元突触效应。 突触后因子 一旦确定了这一点， 将被确定。 将直接检验以下假设：（1）兴奋性和 海马神经元之间的抑制性突触表现不同， 以中等或高频率激活。 (2)神经递质释放 兴奋性和抑制性神经元的特性是实质上不同的。 突触在类似的生理条件下。(3)突触 在培养的海马神经元之间的传递可以通过 量子假说 (4)频率依赖性抑制性衰减 突触效能主要是由于突触前机制。 （五） 兴奋性突触功效的频率依赖性增加是由于 部分是突触前机制。 (6)突触后受体的变化 特性可能有助于频率依赖效应， 更显著地参与兴奋性突触功能的增加。 在这些实验的最后，频率的基础机制- 兴奋性突触的依赖性增强和抑制性突触的依赖性减弱 我们将更好地理解突触。 这样就有可能 将这些发现外推到适当的癫痫模型（切片 制备物或动物模型），以检验这些变化 突触效能是全部或部分负责的过渡， 在癫痫发生区域的癫痫发作和癫痫发作活动的传播 从癫痫病灶转移到正常皮层区域 使用选择性方法 为了防止或逆转这些影响，希望最终， 可以预防或抑制癫痫发作。

The goal of this research is to understand the physiological mechanisms by which excitation and inhibition in the hippocampus can be modulated over relatively short time periods based on patterns of activation of the synapse. It is our hypothesis that the differential modulation of excitatory and inhibitory synaptic efficacy is responsible, at least in part, for the transition between relatively stable interictal activity and seizures and for the spread of seizure activity from areas of focal abnormality to normal areas of CNS. By increasing our understanding of these processes, it is hoped that new strategies for preventing or treating epilepsy will be developed. These experiments will be carried out in a new preparation of very low density dissociated cultures of rat hippocampal neurons. Recording will be made with whole cell patch clamp electrodes from single neurons and from isolated pairs of synaptically connected neurons. The synaptic interactions between the neurons will also be analyzed with histological techniques. The properties of miniature synaptic potentials, both mini- EPSCs and mini-IPSCs, will be examined and it will be determined if they behave as predicted by the quantum hypothesis. Changes in mini-psc amplitude, shape or frequency will be used to help determine if frequency dependent changes in synaptic efficacy are due to presynaptic or postsynaptic factors. Once this is determined, the mechanisms involved will be ascertained. The following hypotheses will be directly tested: (1) Excitatory and inhibitory synapses between hippocampal neurons behave differently when activated at moderate or high frequencies. (2) Neurotransmitter release characteristics are substantially different for excitatory and inhibitory synapses under comparable physiological conditions. (3) Synaptic transmission between hippocampal neurons in culture can be described by the quantum hypothesis. (4) Frequency dependent decrement in inhibitory synaptic efficacy is due predominantly to presynaptic mechanisms. (5) Frequency dependent increment in excitatory synaptic efficacy is due partially to presynaptic mechanisms. (6) Changes in postsynaptic receptor properties may contribute to the frequency dependent effects and this is more prominently involved in the increment of excitatory synaptic function. At the end of these experiments, the mechanisms which underlie frequency- dependent potentiation of excitatory synapses and decrement of inhibitory synapses will be better understood. It will then be possible to extrapolate these findings to an appropriate epilepsy model (a slice preparation or animal model) to test the hypothesis that these changes in synaptic efficacy are responsible in whole, or in part, for the transition to seizures in an epileptogenic area and for the spread of seizure activity from a seizure focus to normal areas of cortex. Using selective methods for preventing or reversing these effects, it is hoped that, ultimately, seizures can be prevented or suppressed.