Spontaneous and evoked vesicle fusion: the emergence of a synapse

大脑中的神经元在称为突触的特殊位置相互通信。在大脑发育过程中，大量神经元(约100亿)通过数量惊人的突触连接(约100万亿)形成大脑。毫不奇怪，神经科学中的一个重要问题是了解突触是如何形成的，以及这些连接是如何将信息从一个神经元传递到另一个神经元的。在突触，信息的传递是通过将突触前神经元释放的神经递质包释放到突触后神经元上的特定受体来完成的。神经递质储存在膜小泡内，通过小泡与质膜的融合释放，从而将神经递质排向突触后神经元。随后从质膜中取回来自囊泡的膜，以用神经递质重新填充并再次循环使用。这里提出的研究将集中于了解突触前终末是如何形成和成熟的，以提供这样一个精细控制的神经递质释放系统。为此，我将使用专门设计的荧光探针，通过每次囊泡与质膜融合时显示荧光闪烁，或通过在囊泡上标记有色颗粒，使其在荧光显微镜下可见，实时报告囊泡的循环。利用这些工具，我将研究突触如何逐渐成熟以释放神经递质，从突触接触形成的最初时刻到神经元成熟的最后阶段。了解这些事件将有助于揭示大脑在发育过程中如何形成连接，并帮助我们了解这一过程出错的神经疾病。

Neurons in the brain communicate with each other at specialized sites called synapses. During brain development a large number of neurons (about 10 billion) make an astonishingly large number of synaptic connections (about 100 trillion) to form a brain. Not surprisingly, an important question in neuroscience is to understand how synapses are formed and how these connections pass information from one neuron to the next. At the synapse, the transfer of information is carried out by the release of packets of neurotransmitter released from a presynaptic neuron onto specific receptors on a postsynaptic neuron. Neurotransmitter is stored inside membrane vesicles and is released by the fusion of vesicles with the plasma membrane, which expels the neurotransmitter towards the postsynaptic neuron. The membrane from the vesicle is subsequently retrieved from the plasma membrane to be refilled with neurotransmitter and recycled for use once again. The research proposed here will focus on understanding how a presynaptic terminal forms and matures to provide such an exquisitely controlled system for releasing neurotransmitter. For this purpose I will use especially designed fluorescent probes that report vesicle cycling in real time by showing flashes of fluorescence every time a vesicle fuses with the plasma membrane or by tagging the vesicle with coloured particles that make them visible under a fluorescent microscope. Exploiting these tools I will study how synapses gradually mature to release neurotransmitter, from the initial moments of the formation of a synaptic contact to the final stages of neuronal maturation. Understanding these events will help uncover how connections in the brain form during development and help us understand neurological diseases where this process has gone wrong.