CA++ & PRESYNAPTIC MODULATION--SYNAPTIC TRANSMISSION

有令人信服的证据表明突触前抑制参与其中。 在控制正常的突触传递和防止过度 哺乳动物中枢突触的神经递质释放。突触前 站点是调节突触传递的有效靶点 突触前电压依赖性钙通道在中枢神经系统中的作用 控制发射机释放。 为了解决我们理解基本突触前的长期目标 哺乳动物突触传递的调控机制 中枢性突触，我们建议研究直接和间接作用 突触前钙在突触传递抑制中的作用 海马CA3/CA1、Mf/CA3和PP/GC兴奋性突触。这是一种体外实验 这项研究将使用海马脑片和光学成像技术。 我们将选择性地为突触前终端加载离子敏感 研究突触前突触静息水平和瞬变的指标 钙和突触前钾。此外，我们将使用电压- 用于测量突触前动作电位的敏感染料。特定阻滞剂 将被用于识别和量化突触前的类型 电压依赖性钙通道参与突触传递。我们 将研究突触前钙在神经调节剂应用中的作用 与假定的抑制性突触前活动有关，并确定 涉及的钙通道及其数量抑制。通过 利用先进的光学技术，拟议的研究将提供新的 以及对哺乳动物突触前调制的重要见解 突触传递。这种洞察力将有助于理解 正常的和病理性的突触传递。过量释放 在癫痫发作期间观察到兴奋性神经递质 在脑部受损之后。通过突触前动作控制这种释放 内源性神经调节剂可能是未来治疗的基础 干预措施。 我们将解决以下具体目标： 1)区分主要海马区突触前VDCC的类型 兴奋性突触。 2)研究大鼠脑内突触前钙离子的静息水平和内流。 突触前抑制诱发的突触传递。

There is compelling evidence for the involvement of presynaptic inhibition in controlling normal synaptic transmission and preventing excessive neurotransmitter release at mammalian central synapses. The presynaptic site is an effective target for modulation of synaptic transmission and presynaptic voltage-dependent calcium channels play a significant role in controlling transmitter release. To address our long-term objective of understanding the basic presynaptic mechanisms underlying modulation of synaptic transmission in mammalian central synapses, we propose to investigate the direct and indirect role of presynaptic calcium during inhibition of synaptic transmission at hippocampal CA3/CA1, MF/CA3 and PP/GC excitatory synapses. This in vitro study will employ hippocampal brain slices and optical imaging techniques. We will selectively load presynaptic terminals with ion-sensitive indicators to investigate resting levels and transients of presynaptic calcium and presynaptic potassium. In addition, we will use voltage- sensitive dyes to measure presynaptic action potentials. Specific blockers will be utilized to identify and quantify the types of presynaptic voltage-dependent calcium channels involved in synaptic transmission. We will study presynaptic calcium during the application of neuromodulators with presumed inhibitory presynaptic action and identify the types of calcium channels involved and their quantitative inhibition. Through the use of advanced optical techniques, the proposed studies will provide new and important insight into the presynaptic modulation of mammalian synaptic transmission. This insight will contribute to the understanding of normal and pathological synaptic transmission. Excessive release of excitatory neurotransmitter has been observed during episodes of epilepsy and after brain damage. Control of this release by presynaptically acting endogenous neuromodulators could be the basis of future therapeutic interventions. We will address the following specific aims: 1) To discriminate the types of presynaptic VDCCs at principal hippocampal excitatory synapses. 2) To investigate resting levels and influx of presynaptic Ca2+ during presynaptic inhibition of evoked synaptic transmission.