2-3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline and gamma-glutamylglycine

In the vestibular periphery neurotransmission between hair cells and primary afferent nerves occurs via specialized ribbon synapses. Type I vestibular hair cells (HCIs) make synaptic contacts with calyx terminals, which enclose most of the HCI basolateral surface. To probe synaptic transmission, whole cell patch-clamp recordings were made from calyx afferent terminals isolated together with their mature HCIs from gerbil crista. Neurotransmitter release was measured as excitatory postsynaptic currents (EPSCs) in voltage clamp. Spontaneous EPSCs were classified as simple or complex. Simple events exhibited a rapid rise time and a fast monoexponential decay (time constant < 1 ms). The remaining events, constituting ~40% of EPSCs, showed more complex characteristics. Extracellular Sr

Topics: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Animals; Benzothiadiazines; Calcium Channel Blockers; Calcium Channels, L-Type; Cells, Cultured; Dipeptides; Excitatory Postsynaptic Potentials; Female; Gerbillinae; Hair Cells, Vestibular; Male; Nifedipine; Quinoxalines; Receptors, AMPA; Strontium; Synapses

The short-term dynamics of synaptic communication between neurons provides neural networks with specific frequency-filter characteristics for information transfer. The direction of short-term synaptic plasticity, that is, facilitation versus depression, is highly dependent on and inversely correlated to the basal release probability of a synapse. Amongst the processes implicated in shaping the release probability, proteins that regulate the docking and priming of synaptic vesicles at the active zone are of special importance. Here, we found that a member of the Munc13 protein family of priming proteins, namely Munc13-2, is essential for normal release probability at hippocampal mossy fiber synapses. Paired pulse and frequency facilitation were strongly increased, whereas mossy fiber long-term potentiation was unaffected in the absence of Munc13-2. In contrast, transmission at 3 other types of hippocampal synapses, Schaffer-collateral, associational-commissural, as well as inhibitory synapses onto CA3 pyramidal neurons was unaffected by the loss of Munc13-2.

Topics: Animals; Animals, Newborn; Calcium; Cyclopropanes; Dipeptides; Electric Stimulation; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; GABA Antagonists; Glycine; Hippocampus; In Vitro Techniques; Intracellular Signaling Peptides and Proteins; Long-Term Potentiation; Mice; Mice, Knockout; Mossy Fibers, Hippocampal; Nerve Tissue Proteins; Neuronal Plasticity; Patch-Clamp Techniques; Pyridazines; Quinoxalines; Synapses

The synaptic response waveform, which determines signal integration properties in the brain, depends on the spatiotemporal profile of neurotransmitter in the synaptic cleft. Here, we show that electrophoretic interactions between AMPA receptor-mediated excitatory currents and negatively charged glutamate molecules accelerate the clearance of glutamate from the synaptic cleft, speeding up synaptic responses. This phenomenon is reversed upon depolarization and diminished when intracleft electric fields are weakened through a decrease in the AMPA receptor density. In contrast, the kinetics of receptor-mediated currents evoked by direct application of glutamate are voltage-independent, as are synaptic currents mediated by the electrically neutral neurotransmitter GABA. Voltage-dependent temporal tuning of excitatory synaptic responses may thus contribute to signal integration in neural circuits.

Topics: Animals; Cells, Cultured; Dendrites; Diffusion; Dipeptides; Excitatory Postsynaptic Potentials; gamma-Aminobutyric Acid; Glutamic Acid; Magnesium; Male; Monte Carlo Method; Patch-Clamp Techniques; Pyramidal Cells; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Receptors, GABA; Synapses

Synapses driven by action potentials are thought to release transmitter in an all-or-none fashion; either one synaptic vesicle undergoes exocytosis, or there is no release. We have estimated the glutamate concentration transient at climbing fiber synapses on Purkinje cells by measuring the inhibition of excitatory postsynaptic currents (EPSCs) produced by a low-affinity competitive antagonist of AMPA receptors, gamma-DGG. The results, together with simulations using a kinetic model of the AMPA receptor, suggest that the peak glutamate concentration at this synapse is dependent on release probability but is not affected by pooling of transmitter released from neighboring synapses. We propose that the mechanism responsible for the elevated glutamate concentration at this synapse is the simultaneous release of multiple vesicles per site.

Topics: Animals; Biological Transport; Calcium; Dipeptides; Excitatory Postsynaptic Potentials; Glutamic Acid; Kinetics; Kynurenic Acid; Neurotransmitter Agents; Purkinje Cells; Quinoxalines; Rats; Receptors, AMPA; Synapses; Synaptic Transmission