@article{1323, abstract = {Mossy fiber synapses on CA3 pyramidal cells are 'conditional detonators' that reliably discharge postsynaptic targets. The 'conditional' nature implies that burst activity in dentate gyrus granule cells is required for detonation. Whether single unitary excitatory postsynaptic potentials (EPSPs) trigger spikes in CA3 neurons remains unknown. Mossy fiber synapses exhibit both pronounced short-term facilitation and uniquely large post-tetanic potentiation (PTP). We tested whether PTP could convert mossy fiber synapses from subdetonator into detonator mode, using a recently developed method to selectively and noninvasively stimulate individual presynaptic terminals in rat brain slices. Unitary EPSPs failed to initiate a spike in CA3 neurons under control conditions, but reliably discharged them after induction of presynaptic short-term plasticity. Remarkably, PTP switched mossy fiber synapses into full detonators for tens of seconds. Plasticity-dependent detonation may be critical for efficient coding, storage, and recall of information in the granule cell–CA3 cell network.}, author = {Vyleta, Nicholas and Borges Merjane, Carolina and Jonas, Peter M}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Plasticity-dependent, full detonation at hippocampal mossy fiber–CA3 pyramidal neuron synapses}}, doi = {10.7554/eLife.17977}, volume = {5}, year = {2016}, } @article{2229, abstract = {The distance between Ca^2+ channels and release sensors determines the speed and efficacy of synaptic transmission. Tight "nanodomain" channel-sensor coupling initiates transmitter release at synapses in the mature brain, whereas loose "microdomain" coupling appears restricted to early developmental stages. To probe the coupling configuration at a plastic synapse in the mature central nervous system, we performed paired recordings between mossy fiber terminals and CA3 pyramidal neurons in rat hippocampus. Millimolar concentrations of both the fast Ca^2+ chelator BAPTA [1,2-bis(2-aminophenoxy)ethane- N,N, N′,N′-tetraacetic acid] and the slow chelator EGTA efficiently suppressed transmitter release, indicating loose coupling between Ca^2+ channels and release sensors. Loose coupling enabled the control of initial release probability by fast endogenous Ca^2+ buffers and the generation of facilitation by buffer saturation. Thus, loose coupling provides the molecular framework for presynaptic plasticity.}, author = {Vyleta, Nicholas and Jonas, Peter M}, issn = {00368075}, journal = {Science}, number = {6171}, pages = {665 -- 670}, publisher = {American Association for the Advancement of Science}, title = {{Loose coupling between Ca^2+ channels and release sensors at a plastic hippocampal synapse}}, doi = {10.1126/science.1244811}, volume = {343}, year = {2014}, } @article{3121, abstract = {Voltage-activated Ca(2+) channels (VACCs) mediate Ca(2+) influx to trigger action potential-evoked neurotransmitter release, but the mechanism by which Ca(2+) regulates spontaneous transmission is unclear. We found that VACCs are the major physiological triggers for spontaneous release at mouse neocortical inhibitory synapses. Moreover, despite the absence of a synchronizing action potential, we found that spontaneous fusion of a GABA-containing vesicle required the activation of multiple tightly coupled VACCs of variable type.}, author = {Williams, Courtney and Chen, Wenyan and Lee, Chia and Yaeger, Daniel and Vyleta, Nicholas and Smith, Stephen}, journal = {Nature Neuroscience}, number = {9}, pages = {1195 -- 1197}, publisher = {Nature Publishing Group}, title = {{Coactivation of multiple tightly coupled calcium channels triggers spontaneous release of GABA}}, doi = {10.1038/nn.3162}, volume = {15}, year = {2012}, } @article{469, abstract = {Spontaneous release of glutamate is important for maintaining synaptic strength and controlling spike timing in the brain. Mechanisms regulating spontaneous exocytosis remain poorly understood. Extracellular calcium concentration ([Ca2+]o) regulates Ca2+ entry through voltage-activated calcium channels (VACCs) and consequently is a pivotal determinant of action potential-evoked vesicle fusion. Extracellular Ca 2+ also enhances spontaneous release, but via unknown mechanisms. Here we report that external Ca2+ triggers spontaneous glutamate release more weakly than evoked release in mouse neocortical neurons. Blockade of VACCs has no effect on the spontaneous release rate or its dependence on [Ca2+]o. Intracellular [Ca2+] slowly increases in a minority of neurons following increases in [Ca2+]o. Furthermore, the enhancement of spontaneous release by extracellular calcium is insensitive to chelation of intracellular calcium by BAPTA. Activation of the calcium-sensing receptor (CaSR), a G-protein-coupled receptor present in nerve terminals, by several specific agonists increased spontaneous glutamate release. The frequency of spontaneous synaptic transmission was decreased in CaSR mutant neurons. The concentration-effect relationship for extracellular calcium regulation of spontaneous release was well described by a combination of CaSR-dependent and CaSR-independent mechanisms. Overall these results indicate that extracellular Ca2+ does not trigger spontaneous glutamate release by simply increasing calcium influx but stimulates CaSR and thereby promotes resting spontaneous glutamate release. }, author = {Vyleta, Nicholas and Smith, Stephen}, journal = {European Journal of Neuroscience}, number = {12}, pages = {4593 -- 4606}, publisher = {Wiley-Blackwell}, title = {{Spontaneous glutamate release is independent of calcium influx and tonically activated by the calcium-sensing receptor}}, doi = {10.1523/JNEUROSCI.6398-10.2011}, volume = {31}, year = {2011}, }