Regulation of calcium-secretion coupling

神经元通过突触相互交流。当动作电位到达突触的突触前侧时，电信号通过突触囊泡的钙依赖性释放转化为化学信号。囊泡含有神经递质，然后穿过突触间隙，并通过打开神经递质门控离子通道在突触后细胞中转化为电信号。这种复杂的化学过程是神经系统中所有通信的基础，并且可能进化为允许突触连接的复杂调制，因为由缝隙连接组成的电连接足以传输电信号。调节这一过程的方式之一是动作电位是否引起突触囊泡的释放。调节递质释放概率的能力是神经系统可塑性的基础。在我们的计划中，我们将阐明基本的机制，通过它的释放是调节使用模型的感觉运动神经元突触的海洋蜗牛。在这种动物中，行为习惯化，即动物忽略无害刺激的能力，是由该突触释放的递质的损失介导的。通过释放5-羟色胺，有害刺激导致习惯化的逆转（通过恢复突触处的递质释放）和敏感化（通过增加突触处的递质释放）。这些突触的调节可以在培养物中研究，其中分子和细胞技术可以应用于确定这种调节的介导机制。这将导致关于如何调节递质释放以及突触如何工作的基本发现。

Neurons communicate with each other at synapses. When the action potential reaches the presynaptic side of the synapse, the electrical signal is turned into a chemical signal through the calcium-dependent release of a synaptic vesicle. The vesicle contains neurotransmitters that then cross the synaptic cleft and are converted into an electrical signal in the postsynaptic cell through opening of neurotransmitter-gated ion channels. This complicated chemical process underlies all communication in the nervous system and presumably evolved to allow sophisticated modulation of synaptic connections, since electrical connections consisting of gap-junctions would be sufficient to just transmit the electrical signal. One of the ways this process is regulated is whether or not the action potential causes release of a synaptic vesicle. The ability to modulate the probability of transmitter release underlies much of the plasticity of the nervous system. In our program, we will elucidate fundamental mechanisms by which release is regulated using the model sensory-motor neuron synapse of the marine snail Aplysia. In this animal, behavioral habituation, the ability of the animal to ignore innocuous stimuli, is mediated by the loss of transmitter release at this synapse. A noxious stimulus, through the release of serotonin, leads both to the reversal of habituation (through regaining transmitter release at the synapse) and sensitization, through increasing transmitter release at this synapse. The modulation of these synapses can be studied in cultures, where molecular and cellular techniques can be applied to determine the mechanisms by which this regulation is mediated. This will lead to fundamental discoveries on how transmitter release is regulated and thus how synapses work.