Synaptic vesicle dynamics: a simple model of phasic release (original) (raw)
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JSIR Vol.79(04) [April 2020], 2020
When a postsynaptic neuron receives a spike from the axon, its synapse releases neurotransmitters to the synaptic cleft. The probability of vesicle release depends on the amount of calcium ions. The concentration of calcium ions keeps on changing with time. The opening and closing of these channels is controlled by the calcium ion gates operating at different rates. Similarly, the binding of neurotransmitters to the membrane depends on the number of receptors. The existing literature considers probabilities of vesicle release and binding of neurotransmitters as constants. In practice, these two probabilities are time-dependent. This issue is addressed in this paper and new derivations of the time-varying nature of these two probabilities are obtained from simulation study and analysis. The present investigation of estimation of these two time-dependent probabilities will help to develop improved nanoscale neuronal communication models.
Mathematical theory of chemical synaptic transmission
Biological Cybernetics, 1990
Mathematical theory of chemical synaptic transmission is suggested in which the modes of operation of chemical synapses are given as consequencies of some fundamental theoretical principles presented in the form of systems of quantum and macroscopic postulates. These postulates establish transmitter transfer rules between 3 component partscytoplasmic, vesicular and external pools of neurotransmitter. The main features of the transfers are determined by special properties of the dividing membranes (synaptic and vesicle) which show high selectivity towards the direction of the transmitter quantum transfer. The formulation of a previously unknown effect of transmitter quantum transfer from the vesicular pool into the cytoplasmic one is introduced: it is postulated that each arriving presynaptic impulse not only releases a constant fraction of the current contents of the cytoplasmic pool into the synaptic cleft (external pool), but also realizes practically simultaneous transmitter transfer from the vesicular pool into the cytoplasmic one. Zone structure of the vesicular pool is postulated. In accordance with basic equations of the theory a nonlinear control system (dynamic synaptic modulator -DYSYM) of transmitter release from the terminal is constructed.
Time-coded neurotransmitter release at excitatory and inhibitory synapses
Proceedings of the National Academy of Sciences of the United States of America, 2016
Communication between neurons at chemical synapses is regulated by hundreds of different proteins that control the release of neurotransmitter that is packaged in vesicles, transported to an active zone, and released when an input spike occurs. Neurotransmitter can also be released asynchronously, that is, after a delay following the spike, or spontaneously in the absence of a stimulus. The mechanisms underlying asynchronous and spontaneous neurotransmitter release remain elusive. Here, we describe a model of the exocytotic cycle of vesicles at excitatory and inhibitory synapses that accounts for all modes of vesicle release as well as short-term synaptic plasticity (STSP). For asynchronous release, the model predicts a delayed inertial protein unbinding associated with the SNARE complex assembly immediately after vesicle priming. Experiments are proposed to test the model's molecular predictions for differential exocytosis. The simplicity of the model will also facilitate large...
A Semiquantitative Theory of Synaptic Vesicle Movements
Biophysical Journal, 1973
Under the assumption that vesicles are the anatomic correlate of quantal release, the forces governing the movement of synaptic vesicles inside neurons are analyzed. Semiquantitative calculations are presented to show that a diffuse layer field penetrates a few Debye lengths into the axoplasm. This field binds tightly a monolayer of water to the membrane forming the potential barrier for miniature end-plate potential (mepp) release. The action potential destroys the monolayer and pulls the vesicle to the membrane. The vesicles are brought to the synaptic zone and held there by a Na+ leak in the synaptic membrane. A stochastic theory of synaptic vesicle release is presented to explain experimental results. The rate of vesicle release is fractionated into a rate of membrane contacts by a vesicle and a rate of vesicle discharge per contact. I would like to express my appreciation to Dr. Motoy Kuno for his help and advice. The development of the compound probability from Vere-Jones was shown to me by Dr. Robert Zucker. I thank him for this and a very helpful critical reading.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002
Monte Carlo simulations were performed on a release model based on experimental data from single glutamatergic synapses containing a single release site in the hippocampal CA1 region of the neonatal rat. These simulations explored what can be learned about the release process by examining how the release probability in response to the second stimulus (P(2)) of a paired stimulus to a synapse depends on the release in response to the first stimulus. Comparisons between experimental data from a number of individual synapses and the simulated data support the notion that the immediately releasable vesicle pool is small (approximately one) and shows substantial intertrial variation. The simulations also show that the release dependence of P(2) is not necessarily an indicator of either intertrial variation in Ca(2+) influx, feedback effects of released transmitter, or activation failure of the axon.
A dual-Ca2+-sensor model for neurotransmitter release in a central synapse
Nature, 2007
Ca 2+-triggered synchronous neurotransmitter release is well described, but asynchronous releasein fact, its very existence-remains enigmatic. Here, we report a quantitative description of asynchronous neurotransmitter release in calyx of Held synapses. We show that deletion of synaptotagmin-2 in mice selectively abolishes synchronous release, allowing us to study pure asynchronous release in isolation. Using photolysis experiments of caged-Ca 2+ , we demonstrate that asynchronous release displays a Ca 2+-cooperativity of ~2 with a Ca 2+-affinity of ~44 µM, in contrast to synchronous release which exhibits a Ca 2+-cooperativity of ~5 with a Ca 2+-affinity of 38 µM. Our results reveal that release triggered in wild-type synapses at low Ca 2+-concentrations is physiologically asynchronous, and that asynchronous release completely empties the readilyreleasable pool of vesicles during sustained elevations in Ca 2+. We propose a two Ca 2+-sensor model of release that quantitatively describes the contributions of synchronous and asynchronous release under different presynaptic Ca 2+-dynamics conditions. List of key genes/proteins synaptotagmin; SNARE proteins; Ca 2+-channel Two modes of Ca 2+-triggered neurotransmitter release were described. Fast synchronous release predominates in all synapses during low-frequency action-potential firing 1,2. Slower asynchronous release mediates synaptic transmission in some synapses during highfrequency action-potential trains 3-7 , but remains a minor component in other synapses 1,2. Precise measurements of Ca 2+-triggering of synchronous release were obtained in the calyx
Diffusion cannot govern the discharge of neurotransmitter in fast synapses
Biophysical Journal, 1994
In the present work we show that dffusion canot provide the observed fast discharge of nroarmTte from a synaptic vesicle du maiy use it is not sufficiently rapid nor is it sufficently temperaturedepedent Modelig dcarge fromn the vesice into dt cleft as a continuous point source, we have determined th discharge should occur in 50-75 ps, to provide the observed high concenaons of at the crical zone.
Neurotransmitter release at rapid synapses
Biochimie, 2000
The classical concept of the vesicular hypothesis for acetylcholine (ACh) release, one quantum resulting from exocytosis of one vesicle, is becoming more complicated than initially thought. 1) synaptic vesicles do contain ACh, but the cytoplasmic pool of ACh is the first to be used and renewed on stimulation. 2) The vesicles store not only ACh, but also ATP and Ca 2+ and they are critically involved in determining the local Ca 2+ microdomains which trigger and control release. 3) The number of exocytosis pits does increase in the membrane upon nerve stimulation, but in most cases exocytosis happens after the precise time of release, while it is a change affecting intramembrane particles which reflects more faithfully the release kinetics. 4) The SNARE proteins, which dock vesicles close to Ca 2+ channels, are essential for the excitation-release coupling, but quantal release persists when the SNAREs are inactivated or absent. 5) The quantum size is identical at the neuromuscular and nerve-electroplaque junctions, but the volume of a synaptic vesicle is eight times larger in electric organ; at this synapse there is enough ACh in a single vesicle to generate 15-25 large quanta, or 150-200 subquanta. These contradictions may be only apparent and can be resolved if one takes into account that an integral plasmalemmal protein can support the formation of ACh quanta. Such a protein has been isolated, characterised and called mediatophore. Mediatophore has been localised at the active zones of presynaptic nerve terminals. It is able to release ACh with the expected Ca 2+-dependency and quantal character, as demonstrated using mediatophore-transfected cells and other reconstituted systems. Mediatophore is believed to work like a pore protein, the regulation of which is in turn likely to depend on the SNARE-vesicle docking apparatus.
Experimental and modeling investigation of the mechanism of synaptic vesicles recycling
Biophysics, 2012
Under the condition of microelectrode recording and fluorescence microscopy with dye FM 1 43 the research of exo /endocytosis of synaptic vesicles in motor nerve terminals (NT) of frog cutaneous pectoris and white mice diaphragm muscles during high frequency stimulation (20 imp/s) was carried out. A mathe matical modeling allowed us to conclude that the obtained experimental data can be explained in the follow ing framework. Three pools of synaptic vesicles are involved in neurotransmitter release in the frog motor NT. Recovery of these pools is provided by endocytosis of two types: fast endocytosis with limited capacity and slow endocytosis. Fast reconstructing vesicles refill the mobilization pool and slow endocytosis recovers the reserve pool. Our modeling investigation has revealed in frog NT independent recruiting of reserve and mobi lization pools to the neurotransmitter secretion, i.e. this pools work concurrently. Experimental data, obtained on mice preparations, are well described with the framework of two pools model including single type of endocytosis (fast endocytosis).