Presynaptic calcium, neurotransmitter release and modulation

神经元在称为突触的特殊接触部位相互交流。在突触处，神经递质物质从“突触前”神经元分泌，并扩散一小段距离以结合到“突触后”目标上的受体，该目标可以是另一个神经元、分泌腺或肌肉。这些受体的激活启动构成神经元间信号的电和/或生物化学事件。 递质释放是一个高度调节的过程，其受突触前末梢中钙离子（Ca 2+）浓度的变化控制。神经回路需要精确控制分泌的时间和调节发射量，才能正确处理信息。 为了启动快速、高度调节的释放，Ca 2+通过与包含和释放递质的囊泡紧密共定位的Ca 2+通道进入突触前末梢。 Ca ~（2+）内流与囊泡融合之间的密切关系意味着Ca ~（2+）通道调节是调节突触连接强度的有效途径。 除了直接驱动囊泡融合外，Ca 2+还通过多种生化途径发挥作用，以调节传播的功效。 大多数神经和神经肌肉疾病可以追溯到功能失调的突触传递。在许多情况下，神经功能的正常调节，如对恒定刺激的适应或短期和长期的学习和记忆，是由突触连接强度的变化引起的。因此，重要的是要非常详细地了解突触传递的过程及其调节，以了解正常的大脑功能，并合理地设计治疗策略来治疗神经系统疾病。 我们使用电生理和荧光成像技术的组合，包括Ca 2+敏感染料的成像和应用蜗牛和蜘蛛毒素阻断Ca 2+通道来研究Ca 2+流入和释放之间的关系，以确定驱动释放的Ca 2+通道的亚型，并阐明神经调节物质如5-羟色胺，多巴胺通过突触前末梢上的受体调节释放。

Neurons communicate with each other at specialized sites of contact called synapses. At synapses a neurotransmitter substances is secreted from the "preysnaptic" neuron and diffuses a short distance to bind to receptors on the "postsynaptic" target, which can be another neuron, a secretory gland or a muscle. Activation of these receptors initiates electrical and/or biochemical events that constitute the inter-neuronal signal. Transmitter release is a highly regulated process that is controlled by changes in calcium ion (Ca2+) concentration in the presynaptic terminal. Precise control of the timing and regulation of the amount of transmitter that is secreted is needed for neural circuits to process information properly. To initiate rapid, highly regulated release, Ca2+ enters the presynaptic terminal through Ca2+ channels that are tightly colocalized with vesicles that contain and release the transmitter. The intimate relationship between Ca2+ influx and vesicle fusion means that Ca2+ channel regulation is an effective way to modulate synaptic connection strength. As well as driving vesicle fusion directly, Ca2+ acts through a variety of biochemical pathways to modulate the efficacy of transmission. The majority of neurological and neuromuscular disorders can be traced to dysfunctional synaptic transmission. In many cases normal modulation of neural function such as adaptation to constant stimuli or short and long-term learning and memory are caused by changes in synaptic connection strength. It is therefore important to understand in great detail the processes of synaptic transmission and their regulation in order to understand normal brain function and to rationally design therapeutic strategies to treat neurological disorders. We use a combination of electrophysiological and fluorescence imaging techniques, including imaging of Ca2+ sensitive dyes and applying snail and spider toxins to block Ca2+ channels to study the relationship between Ca2+ influx and release, to determine the sub-types of Ca2+ channels that are driving release and to elucidate the mechanisms whereby neuromodulatory substances such as serotonin, and dopamine regulate release through receptors on presynaptic terminals.