The Experts below are selected from a list of 213 Experts worldwide ranked by ideXlab platform
Wade G. Regehr - One of the best experts on this subject based on the ideXlab platform.
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the influence of multivesicular release and Postsynaptic Receptor saturation on transmission at granule cell to purkinje cell synapses
The Journal of Neuroscience, 2005Co-Authors: Kelly A Foster, John J Crowley, Wade G. RegehrAbstract:The properties of a synapse are crucially dependent on whether an action potential can trigger the release of multiple vesicles at an individual release site [multivesicular release (MVR)] and whether fusion of a single vesicle leads to Receptor saturation. MVR and Receptor saturation both occur at some high p synapses, but it is not known whether they also occur at low p synapses. Here we examine this issue at the low p synapse between parallel fibers and Purkinje cells using the low-affinity antagonist DGG (γ-d-glutamylglycine) to relieve AMPA Receptor saturation. We find that the presence of MVR and Receptor saturation at this synapse alters the calcium dependence of synaptic transmission and reduces the extent of facilitation. These findings establish that MVR and Postsynaptic Receptor saturation can influence transmission even at synapses with a low initial probability of release and suggest that these properties may be common at synapses in the mammalian brain.
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Interaction of Postsynaptic Receptor Saturation with Presynaptic Mechanisms Produces a Reliable Synapse
Neuron, 2002Co-Authors: Kelly A Foster, Anatol C. Kreitzer, Wade G. RegehrAbstract:Synapses that reliably activate their Postsynaptic targets typically release neurotransmitter with high probability, are not very sensitive to changes in calcium entry, and depress. We have determined the mechanisms that give rise to these characteristic features at the climbing fiber to Purkinje cell synapse. We find that saturation of presynaptic calcium entry, of presynaptic release, and of Postsynaptic Receptors combine to produce a Postsynaptic response that is near maximal. Postsynaptic Receptor saturation also accelerates recovery from depression, in part by accentuating a rapid calcium-dependent recovery phase. Thus, Postsynaptic Receptor saturation interacts with presynaptic mechanisms to produce highly reliable synapses that can effectively drive their targets even during sustained activation.
Kelly A Foster - One of the best experts on this subject based on the ideXlab platform.
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the influence of multivesicular release and Postsynaptic Receptor saturation on transmission at granule cell to purkinje cell synapses
The Journal of Neuroscience, 2005Co-Authors: Kelly A Foster, John J Crowley, Wade G. RegehrAbstract:The properties of a synapse are crucially dependent on whether an action potential can trigger the release of multiple vesicles at an individual release site [multivesicular release (MVR)] and whether fusion of a single vesicle leads to Receptor saturation. MVR and Receptor saturation both occur at some high p synapses, but it is not known whether they also occur at low p synapses. Here we examine this issue at the low p synapse between parallel fibers and Purkinje cells using the low-affinity antagonist DGG (γ-d-glutamylglycine) to relieve AMPA Receptor saturation. We find that the presence of MVR and Receptor saturation at this synapse alters the calcium dependence of synaptic transmission and reduces the extent of facilitation. These findings establish that MVR and Postsynaptic Receptor saturation can influence transmission even at synapses with a low initial probability of release and suggest that these properties may be common at synapses in the mammalian brain.
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Interaction of Postsynaptic Receptor Saturation with Presynaptic Mechanisms Produces a Reliable Synapse
Neuron, 2002Co-Authors: Kelly A Foster, Anatol C. Kreitzer, Wade G. RegehrAbstract:Synapses that reliably activate their Postsynaptic targets typically release neurotransmitter with high probability, are not very sensitive to changes in calcium entry, and depress. We have determined the mechanisms that give rise to these characteristic features at the climbing fiber to Purkinje cell synapse. We find that saturation of presynaptic calcium entry, of presynaptic release, and of Postsynaptic Receptors combine to produce a Postsynaptic response that is near maximal. Postsynaptic Receptor saturation also accelerates recovery from depression, in part by accentuating a rapid calcium-dependent recovery phase. Thus, Postsynaptic Receptor saturation interacts with presynaptic mechanisms to produce highly reliable synapses that can effectively drive their targets even during sustained activation.
Kendal Broadie - One of the best experts on this subject based on the ideXlab platform.
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Developmental regulation of glutamate Receptor field size by nonvesicular glutamate release
Nature Neuroscience, 2002Co-Authors: David E. Featherstone, Emma Rushton, Kendal BroadieAbstract:We hypothesized that presynaptic glutamate regulates Postsynaptic ionotropic glutamate Receptor number during synaptogenesis. To test this idea, we genetically manipulated presynaptic glutamate levels at the glutamatergic Drosophila neuromuscular junction (NMJ), then microscopically and electrophysiologically measured Postsynaptic glutamate Receptor field size and function. Our data show that presynaptic glutamate is a strong negative regulator of Postsynaptic Receptor field size and function during development. Glutamate-triggered Receptor downregulation was not affected by block of synaptic vesicle fusion, demonstrating that Receptors are regulated by nonvesicular glutamate release. Our results reveal an elegant mechanism for Receptor field regulation during synaptogenesis and reveal a nonpathological role for nonvesicular glutamate release at the synapse.
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Establishing and sculpting the synapse in Drosophila and C. elegans.
Current opinion in neurobiology, 2002Co-Authors: Kendal Broadie, Janet E. RichmondAbstract:Genetic approaches in flies and worms continue to dissect the intricate molecular machinery of chemical synapses. Investigations carried out in the last year provide important new insights into the development and modulation of the presynaptic active zones and Postsynaptic Receptor fields mediating synaptic function. Mutant screens have identified overlapping gene classes mediating synaptogenesis. The leucocyte common antigen-related Receptor tyrosine phosphatase interacts with liprin in the formation of the active zone. Spectrins are essential for the spatial restriction of synaptic proteins to define active zones. Glutamate acts as a negative regulator of its cognate Postsynaptic Receptor to sculpt Receptor field size. Finally, protein translation and degradation regulation emerge as possible key regulators of synaptic efficacy.
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Presynaptic glutamic acid decarboxylase is required for induction of the Postsynaptic Receptor field at a glutamatergic synapse.
Neuron, 2000Co-Authors: David E. Featherstone, Emma Rushton, M Hilderbrand-chae, A.m Phillips, F.r Jackson, Kendal BroadieAbstract:We have systematically screened EMS-mutagenized Drosophila for embryonic lethal strains with defects in glutamatergic synaptic transmission. Surprisingly, this screen led to the identification of several alleles with missense mutations in highly conserved regions of Dgad1. Analysis of these gad mutants reveals that they are paralyzed owing to defects in glutamatergic transmission at the neuromuscular junction. Further electrophysiological and immunohistochemical examination reveals that these mutants have greatly reduced numbers of Postsynaptic glutamate Receptors in an otherwise morphologically normal synapse. By overexpressing wild-type Dgad1 in selected neurons, we show that GAD is specifically required in the presynaptic neuron to induce a Postsynaptic glutamate Receptor field, and that the level of Postsynaptic Receptors is closely dependent on presynaptic GAD function. These data demonstrate that GAD plays an unexpected role in glutamatergic synaptogenesis.
Joel P. Gallagher - One of the best experts on this subject based on the ideXlab platform.
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direct muscarinic and nicotinic Receptor mediated excitation of rat medial vestibular nucleus neurons in vitro
Synapse, 1992Co-Authors: Kevin D. Phelan, Joel P. GallagherAbstract:We have utilized intracellular recording techniques to investigate the cholinoceptivity of rat medial vestibular nucleus (MVN) neurons in a submerged brain slice preparation. Exogenous application of the mixed cholinergic agonists, acetylcholine (ACh) or carbachol (CCh), produced predominantly membrane depolarization, induction of action potential firing, and decreased input resistance. Application of the selective muscarinic Receptor agonist muscarine (MUSC), or the selective nicotinic Receptor agonists nicotine (NIC) or 1,1-dimethyl-4-phenylpiperazinium (DMPP) also produced membrane depolarizations. The MUSC-induced depolarization was accompanied by decreased conductance, while an increase in conductance appeared to underlie the NIC- and DMPP-induced depolarizations. The muscarinic and nicotinic Receptor mediated depolarizations persisted in tetrodotoxin and/or low Ca2+/high Mg2+ containing media, suggesting direct Postsynaptic Receptor activation. The MUSC-induced depolarization could be reversibly blocked by the selective muscarinic-Receptor antagonist, atropine, while the DMPP-induced depolarization could be reversibly suppressed by the selective ganglionic nicotinic-Receptor antagonist, mecamylamine. Some neurons exhibited a transient membrane hyperpolarization during the depolarizing response to CCh or MUSC application. This transient inhibition could be reversibly blocked by the gamma-aminobutyric acid (GABA) antagonist, bicuculline, suggesting that the underlying hyperpolarization results indirectly from the endogenous release of GABA acting at GABA Receptors. This study confirms the cholinoceptivity of MVN neurons and establishes that individual MVN cells possess muscarinic as well as nicotinic Receptors. The data provide support for a prominent role of cholinergic mechanisms in the direct and indirect regulation of the excitability of MVN neurons.
Elise F Stanley - One of the best experts on this subject based on the ideXlab platform.
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transglial transmission at the dorsal root ganglion sandwich synapse glial cell to Postsynaptic neuron communication
European Journal of Neuroscience, 2013Co-Authors: Gabriela M Rozanski, Qi Li, Elise F StanleyAbstract:: The dorsal root ganglion (DRG) contains a subset of closely-apposed neuronal somata (NS) separated solely by a thin satellite glial cell (SGC) membrane septum to form an NS-glial cell-NS trimer. We recently reported that stimulation of one NS with an impulse train triggers a delayed, noisy and long-lasting response in its NS pair via a transglial signaling pathway that we term a 'sandwich synapse' (SS). Transmission could be unidirectional or bidirectional and facilitated in response to a second stimulus train. We have shown that in chick or rat SS the NS-to-SGC leg of the two-synapse pathway is purinergic via P2Y2 Receptors but the second SGC-to-NS synapse mechanism remained unknown. A noisy evoked current in the target neuron, a reversal potential close to 0 mV, and insensitivity to calcium scavengers or G protein block favored an ionotropic Postsynaptic Receptor. Selective block by D-2-amino-5-phosphonopentanoate (AP5) implicated glutamatergic transmission via N-methyl-d-aspartate Receptors. This agent also blocked NS responses evoked by puff of UTP, a P2Y2 agonist, directly onto the SGC cell, confirming its action at the second synapse of the SS transmission pathway. The N-methyl-d-aspartate Receptor NR2B subunit was implicated by block of transmission with ifenprodil and by its immunocytochemical localization to the NS membrane, abutting the glial septum P2Y2 Receptor. Isolated DRG cell clusters exhibited daisy-chain and branching NS-glial cell-NS contacts, suggestive of a network organization within the ganglion. The identification of the glial-to-neuron transmitter and Receptor combination provides further support for transglial transmission and completes the DRG SS molecular transmission pathway.