2-3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline and (1-2-5-6-tetrahydropyridin-4-yl)methylphosphinic-acid

Synapses in the inner plexiform layer of the retina undergo short-term plasticity that may mediate different forms of adaptation to regularities in light stimuli. Using patch-clamp recordings from axotomized goldfish Mb bipolar cell (BC) terminals with paired-pulse light stimulation, we isolated and quantified the short-term plasticity of GABAergic lateral IPSCs (L-IPSCs). Bright light stimulation evoked ON and OFF L-IPSCs in axotomized BCs, which had distinct onset latencies (∼50-80 and ∼70-150 ms, respectively) that depended on background light adaptation. We observed plasticity in both the synaptic strength and latency of the L-IPSCs. With paired light stimulation, latencies of ON L-IPSCs increased at paired-pulse intervals (PPIs) of 50 and 300 ms, whereas OFF L-IPSC latencies decreased at the 300 ms PPI. ON L-IPSCs showed paired-pulse depression at intervals <1 s, whereas OFF L-IPSCs showed depression at intervals ≤1 s and amplitude facilitation at longer intervals (1-2 s). This biphasic form of L-IPSC plasticity may underlie adaptation and sensitization to surround temporal contrast over multiple timescales. Block of retinal signaling at GABA(A)Rs and AMPARs differentially affected ON and OFF L-IPSCs, confirming that these two types of feedback inhibition are mediated by distinct and convergent retinal pathways with different mechanisms of plasticity. We propose that these plastic changes in the strength and timing of L-IPSCs help to dynamically shape the time course of glutamate release from ON-type BC terminals. Short-term plasticity of L-IPSCs may thus influence the strength, timing, and spatial extent of amacrine and ganglion cell inhibitory surrounds.

Topics: Anesthetics, Local; Animals; Axotomy; Biophysical Phenomena; Drug Interactions; Electric Stimulation; Excitatory Amino Acid Antagonists; GABA Antagonists; Goldfish; In Vitro Techniques; Inhibitory Postsynaptic Potentials; Light; Neural Inhibition; Neuronal Plasticity; Patch-Clamp Techniques; Phosphinic Acids; Photons; Presynaptic Terminals; Pyridazines; Pyridines; Quinoxalines; Reaction Time; Retina; Retinal Bipolar Cells; Tetrodotoxin; Time Factors

NG2 cells, oligodendrocyte precursors, play a critical role in myelination during postnatal brain maturation, but a pool of these precursors is maintained in the adult and recruited to lesions in demyelinating diseases. NG2 cells in immature animals have recently been shown to receive synaptic inputs from neurons, and these have been assumed to persist in the adult. Here, we investigated the GABAergic synaptic activity of NG2 cells in acute slices of the barrel cortex of NG2-DsRed transgenic mice during the first postnatal month, which corresponds to the period of active myelination in the neocortex. Our data demonstrated that the frequency of spontaneous and miniature GABAergic synaptic activity of cortical NG2 cells dramatically decreases after the second postnatal week, indicating a decrease in the number of synaptic inputs onto NG2 cells during development. However, NG2 cells still receive GABAergic inputs from interneurons in the adult cortex. These inputs do not rely on the presence of functional synapses but involve a form of GABA spillover. This GABA volume transmission allows interneurons to induce phasic responses in target NG2 cells through the activation of extrasynaptic GABA(A) receptors. Hence, after development is complete, volume transmission allows NG2 cells to integrate neuronal activity patterns at frequencies occurring during in vivo sensory stimulation.

Topics: Age Factors; Animals; Animals, Newborn; Biophysics; Calcium; Cell Line, Transformed; Cerebral Cortex; Electric Conductivity; Excitatory Amino Acid Antagonists; gamma-Aminobutyric Acid; In Vitro Techniques; Interneurons; Luminescent Proteins; Lysine; Mice; Mice, Transgenic; Neurotransmitter Uptake Inhibitors; Nipecotic Acids; Oligodendroglia; Oximes; Patch-Clamp Techniques; Phosphinic Acids; Pyridazines; Pyridines; Quinoxalines; Statistics, Nonparametric; Stem Cells; Synapses; Synaptic Transmission

Although multiple kinetic components of synaptic vesicle endocytosis have been identified, it has remained unclear whether neurons can differentially modulate these components. Using membrane capacitance measurements from isolated goldfish bipolar cell terminals, we found that the kinetics of endocytosis in retinal slices (single exponential decay; tau > 10 s) were significantly slower than those in acutely dissociated terminals (double exponential decay; tau(fast) approximately 1-2 s; tau(slow) > 10 s). Surprisingly, GABA(A) and/or GABA(C) receptor antagonists restored the fast component of endocytosis to terminals in retinal slices. Blocking GABAergic feedback from reciprocal synapses or removing external Cl(-) ions also allowed for fast endocytosis. Elevating internal Cl(-) via the patch pipette invariably slowed endocytosis, even in terminals dialyzed with increased Ca(2+) buffer. These results suggest a new role for GABA and Cl(-) ions in blocking the trigger for fast endocytosis at this ribbon-type synapse.

Topics: Animals; Bicuculline; Calcium; Cells, Cultured; Chelating Agents; Chlorides; Dose-Response Relationship, Drug; Drug Interactions; Egtazic Acid; Endocytosis; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; GABA Antagonists; gamma-Aminobutyric Acid; Goldfish; In Vitro Techniques; Ionophores; Membrane Potentials; Microscopy, Electron, Transmission; Models, Neurological; Neural Inhibition; Neurons; Nystatin; Patch-Clamp Techniques; Phosphinic Acids; Picrotoxin; Presynaptic Terminals; Pyridines; Quinoxalines; Retina; Time Factors; Valine