2-3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline and 2-(2-3-dicarboxycyclopropyl)glycine

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

1. Depolarization-induced suppression of inhibition (DSI) is a form of synaptic plasticity which involves a retrograde messenger. We have performed experiments in Purkinje cells of rat cerebellar slices to determine the nature of this messenger. 2. DSI is mimicked by 2-(2,3-dicarboxycyclopropyl)-glycine (DCG-IV), a specific agonist of group II metabotropic glutamate receptors (mGluRs). 3. DSI is reduced if transmitter release is inhibited by saturating doses of DCG-IV. 4. Both DSI and DCG-IV-induced inhibition are inhibited by L-2-amino-3-phosphonopropionic acid (L-AP3), a drug which interferes with several subtypes of mGluRs. 5. DSI is reduced if synaptic activity is enhanced by application of forskolin. 6. We propose that glutamate or a glutamate-like substance is the retrograde messenger implicated in DSI, and that the inhibition resulting from presynaptic glutamate binding is mediated by a decrease in the presynaptic concentration of cAMP.

Topics: 2-Amino-5-phosphonovalerate; Alanine; Animals; Benzoates; Colforsin; Cyclopropanes; Electrophysiology; Excitatory Amino Acid Antagonists; Glutamic Acid; Glycine; Interneurons; Kinetics; Presynaptic Terminals; Purkinje Cells; Quinoxalines; Rats; Receptors, Metabotropic Glutamate; Synapses; Synaptic Transmission; Tetrodotoxin