CALCIUM AND PRESYNAPTIC MODULATION OF SYNAPTIC TRANSMISS

有令人信服的证据表明突触前抑制的参与 在控制正常的突触传递和防止过度的 哺乳动物中枢突触释放神经递质。突触前 位点是调节突触传递有效靶点， 突触前电压依赖性钙离子通道在神经元的突触前活动中起重要作用， 控制发射器释放。 为了实现我们的长期目标， 哺乳动物突触传递的调节机制 中央突触，我们建议调查的直接和间接的作用， 突触前钙在抑制突触传递过程中的作用 海马CA3/CA1、MF/CA3和PP/GC兴奋性突触。该体外 研究将采用海马脑切片和光学成像技术。 我们将选择性地在突触前末梢装载离子敏感的 研究突触前神经元的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- 敏感染料来测量突触前动作电位。特异性阻断剂 将被用来识别和量化突触前的类型， 参与突触传递的电压依赖性钙通道。我们 将研究突触前钙在神经调质的应用 与假定的抑制性突触前作用，并确定类型的 参与的钙通道及其定量抑制。通过 利用先进的光学技术，拟议的研究将提供新的 对哺乳动物突触前调制的重要见解 突触传递这种见解将有助于理解 正常和病理性突触传递过度释放 在癫痫发作期间观察到兴奋性神经递质 以及脑损伤后通过突触前作用控制这种释放 内源性神经调质可能是未来治疗的基础。 干预措施。 我们将致力于实现以下具体目标： 1)辨别主海马突触前VDCC的类型 兴奋性突触 2)为了研究静息水平和突触前Ca2+内流， 诱发性突触传递的突触前抑制。

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.