Presynaptic morphology and vesicular composition determine vesicle dynamics in mouse central synapses

• Published in: eLife Vol. 6
• Main Authors: Guillaud, Laurent, Dimitrov, Dimitar, Takahashi, Tomoyuki
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 22.04.2017; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Animals; Biological Transport; Cell Biology; Datasets; Experiments; Glutamic acid transporter; Hippocampus; Hippocampus - cytology; Labeling; Localization; Mice; Microscopy; microtubule; Microtubules - metabolism; Mobility; morphology; Nerve endings; Neural circuitry; Neuroscience; Neurotransmission; Optical Imaging; Physiological aspects; presynaptic terminal; Quantum dots; Regulation; Software; Statistical analysis; Synapses; Synapses - physiology; synaptic vesicle; Synaptic vesicles; Synaptic Vesicles - metabolism; vesicular glutamate transporter; microtubule; mouse; mobility; cell biology; morphology; vesicular glutamate transporter; neuroscience; presynaptic terminal; synaptic vesicle
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.24845

Transport of synaptic vesicles (SVs) in nerve terminals is thought to play essential roles in maintenance of neurotransmission. To identify factors modulating SV movements, we performed real-time imaging analysis of fluorescently labeled SVs in giant calyceal and conventional hippocampal terminals. Compared with small hippocampal terminals, SV movements in giant calyceal terminals were faster, longer and kinetically more heterogeneous. Morphological maturation of giant calyceal terminals was associated with an overall reduction in SV mobility and displacement heterogeneity. At the molecular level, SVs over-expressing vesicular glutamate transporter 1 (VGLUT1) showed higher mobility than VGLUT2-expressing SVs. Pharmacological disruption of the presynaptic microtubule network preferentially reduced long directional movements of SVs between release sites. Functionally, synaptic stimulation appeared to recruit SVs to active zones without significantly altering their mobility. Hence, the morphological features of nerve terminals and the molecular signature of vesicles are key elements determining vesicular dynamics and movements in central synapses. In the brains of mammals, communication between cells called neurons is vital for learning and memory. Pairs of neurons communicate at junctions called synapses. At a synapse, the first neuron releases chemical messengers into the gap between the cells, which then bind to and activate receptor proteins on the surface of the second neuron. The chemical messengers are released from bubble-like packages called synaptic vesicles that fuse with the first neuron’s membrane and empty their contents into the synapse. This same neuron then retrieves and reassembles the components of the vesicle, ready to be filled again with the chemical messengers. Neurons must continually retrieve and refill vesicles in order to continue transmitting information at synapses. But while the mechanisms of vesicle fusion and retrieval are well characterized, it remains unclear what triggers the movement and supply of vesicles inside synapses or how these processes are regulated. Deciphering these mechanisms will help us better understand how synapses work in healthy as well as diseased brains. Using high-resolution microscopy, Guillaud et al. have now studied the movements of fluorescently labeled vesicles inside mouse brain synapses grown in the laboratory. This revealed that synaptic vesicles move in much more varied and complex ways than previously thought. The movement of vesicles changed depending on the type and developmental stage of the synapses. It also depended on the identity of particular proteins within the membranes of the vesicles themselves. These proteins, known as transporters, enable vesicles to take up the chemical messengers. Vesicles with different transporters showed different patterns of movement. Disrupting components of the internal skeleton of the neuron – specifically protein filaments called microtubules – also disrupted vesicle movement. By contrast, changes in the activity level of the synapse had no such effect. The next step is to determine exactly how these factors regulate the movement of vesicles at synapses. Studies can then examine whether these processes are disrupted in neurological disorders, in which communication at synapses is often impaired.