Synaptic vesicle pools

The pharmacology of the presynaptic Ca + channels in the reticulospinal synapse has been 

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One characteristic of regulated exocytosis is the ability to store secretory vesicles in a reserve pool for utilization upon stimulation. In the presynaptic terminal, this principle is expanded to define multiple pools of synaptic vesicles a ready releasable pool, a recycled synaptic vesicle pool and a larger reserve pool. This reserve pool assures that neurotransmitter is available for release in response to even the highest physiological demands. Neurons can fire so many times per minute because synaptic vesicles from the ready releasable pool at a given synapse undergo exocytosis in response to a single action potential. 

Rizzoli SO, Betz WJ (2005) Synaptic vesicle pools. Nat Rev Neurosci 6 57-69 Roos J, Kelly RB (1999) The endocytic machinery in nerve terminals surrounds sites of exocytosis. Curr Biol 9 1411-14... 

Leenders AGM, Scholten G, De Lange RPJ, Lopes Da Silva FH, Ghijsen WEJM. 2002. Sequential changes in synaptic vesicle pools and endosome-like organelles during depolarization near the active zone of central nerve terminals. Neuroscience 109 195-206. 

Rizzoli SO, Betz WJ. 2005. Synaptic vesicle pools. Nat Rev Neurosci 6 57-69. 

Morciano, M., Burre, J., Corvey, C., Karas, M., Zimmermann, H. and Volknandt, W. (2005) Iimnunoiso-lation of two synaptic vesicle pools from synaptosomes a proteomics analysis. J. Neurochem. 95, 1732-1745. 

The third and largest synaptic vesicle pool is termed the reserve pool and does not contribute to neurotransmitter release under normal physiological conditions. It is proposed that reserve pool vesicles are only recruited with extremely intense extended bouts of synaptic stimulation, conditions under which the recycling pool of vesicles is depleted (17). When vesicle pool sizes are expressed as percentages of the total synaptic vesicle cluster, these percentages hold well across many synapse... 

Lamprey giant reticulospinal axon 5. SYNAPTIC VESICLE POOLS... 

Fig. 4. Disruption of the synapsin-dependent vesicle pool by presynaptic microinjection of synapsin antibodies in the lamprey reticulospinal synapse. (A) Electron micrograph of a control synapse. (B) A synapse in an axon injected with synapsin antibodies. The axon was lightly stimulated (1 Hz for 12 min) and allowed to rest for 90 min before fixation. Note that a narrow rim of vesicles remains in the antihody-injected synapse. (O Immunogold staining of a reticulospinal synapse with synapsin antibodies. Note that the vesicles adjacent to the presynaptic membrane are almost devoid of gold particles. (D) Visualization of the filamentous cytomatrix that overlaps with the synaptic vesicle pool that remains after perturbation of synapsins. The electron micrograph shows a synapse in a normal axon (i.e. no microinjection or stimulation had been performed) stained with phosphotungstic acid (Gustafsson et al., 1996). The filamentous eytomatrix (arrowheads) at the presynaptic membrane is visible, but not the synaptic vesicle cluster. Designations as in Fig. 1. Scale bar, 0.2 p.m. Reprinted from Brodin et al. (1995) Eur J Neurosci 9 2503-2511, with permission.

NMJs at type IIx and/or Ilb fibers. Moreover, the extent of overlap between pre- and postsynaptic components of the NMJ was lower at type I muscle fibers in hypothyroid compared to control animals. No studies have specifically examined the effects of hypothyroidism (either as a result of low-iodine diets or other conditions) on the ultrastructure of NMJs or the size of synaptic vesicle pools. 

Synaptic vesicles are the organelles in axon terminals that store neurotransmitters and release them by exocytosis. There are two types, the large dense-core vesicles, diameter about 90 nm, that contain neuropeptides, and the small synaptic vesicles, diameter about 50nm, that contain non-peptide transmitters. About ten vesicles per synapse are docked to the plasma membrane and ready for release, the readily releasable pool . Many more vesicles per synapse are stored farther away from the plasma membrane, the resting pool . When needed, the latter vesicles may be recruited into the readily releasable pool. Neuronal depolarization and activation of voltage-sensitive Ca2+... 

Those vesicles have been primed by docking at the active zone and are therefore ready for exocytosis upon arrival of an action potential. However, for the synapse to respond rapidly and repeatedly under heavy physiological demand, these exocytosed vesicles must be rapidly replaced. This is accomplished first from the recycled pool of vesicles and, as the demand increases, from the reserve pool. To be recycled, synaptic vesicles must be reloaded quickly after they release their contents. The sequence of events that is triggered by neurotransmitter exocytosis is known as the synaptic vesicle cycle [73,74] (Fig. 9-8). 

FIGURE 2 3-7 Schematic diagram of the synaptic vesicle cycle. Neurotransmitter-filled vesicles held in the reserve pool are trafficked to a readily releasable pool where they are docked, primed and fused with the plasmalemma at the synaptic cleft. Also depicted is the clathrin-mediated endocy-tosis of the fused vesicles, which is followed by their uncoating and recycling via early endosomal fusion and budding of vesicles. This returns the vesicles to the reserve pool. Some of the phosphoproteins which regulate these steps are shown. For a more detailed description of this process and the phosphoproteins involved the reader is directed to the excellent text by Cowen et al. [67]. 

Inactivation of the a-synuclein gene by homologous recombination results in mice that appear largely normal [3]. Analysis of mice lacking y-synuclein has similarly failed to reveal any gross abnormalities [4]. In hippocampal slices from mice without a-synuclein, the replenishment of docked vesicles by reserve pool vesicles was slower than in slices from control mice. It suggests a physiological role for a-synuclein in the mobilization of synaptic vesicles. 

Turner TJ (2004) Nicotine enhancement of dopamine release by a calcium-dependent increase in the size of the readily releasable pool of synaptic vesicles. J Neurosci 24 11328-11336 Unwin N (1995) Acetylcholine receptor channel imaged in the open state. Nature 373 37-43 Unwin N (2003) Structure and action of the nicotinic acetylcholine receptor explored by electron microscopy. FEBS Lett 555 91-95... 

Mozhayeva MG, Sara Y, Liu X, Kavalali ET (2002) Development of vesicle pools during maturation of hippocampal synapses. J Neurosci 22 654-65 Murthy VN, Stevens CF (1998) Synaptic vesicles retain their identity through the endocytic cycle. Nature 392 497-501... 

Roseth S, Fykse EM, Fonnum F (1995) Uptake of L-glutamate into rat brain synaptic vesicles effect of inhibitors that bind specifically to the glutamate transporter. J Neurochem 65 96-103 Ryan TA (1996) Endocytosis at nerve terminals timing is everything. Neuron 17 1035-7 Ryan TA, Smith SJ (1995) Vesicle pool mobilization during action potential firing at hippocampal synapses. Neuron 14 983-9... 

In addition to the proteins discussed above, neuronal SNAREs were reported to interact with numerous other proteins in a specific manner, but in most cases both the structural basis and the biological function of these interactions need to be defined. For instance, synaptophysin, a membrane protein of synaptic vesicles, forms a complex with synaptobrevin in which synaptobrevin is not available for interactions with its partner SNAREs syntaxin 1A and SNAP-25, suggesting that this complex represents a reserve pool of recruitable synaptobrevin (Becher et al. 1999) or regulates interactions between the vesicle-associated synaptobrevin and the plasmalem-mal SNAREs. Alternatively, it has been suggested that this complex is involved in synaptobrevin sorting to synaptic vesicles. 

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