neuropeptide-y and 2-3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline

Depolarization by the neurotransmitter GABA regulates adult neurogenesis. We found interneurons of the neurogliaform cell family to be a primary source of GABA for newborn neurons in mouse dentate gyrus. GABAergic depolarization occurred in concert with reduced synaptic inhibition of mature neurons, suggesting that the local circuitry coordinates the activation of new and pre-existing cells.

Topics: Action Potentials; Animals; Animals, Newborn; Bacterial Proteins; Biophysical Phenomena; Cell Adhesion Molecules, Neuronal; Electric Stimulation; Excitatory Amino Acid Antagonists; Extracellular Matrix Proteins; GABA Antagonists; Glutamic Acid; Green Fluorescent Proteins; Interneurons; Iontophoresis; Luminescent Proteins; Lysine; Mice; Mice, Inbred C57BL; Mice, Transgenic; Models, Neurological; Nerve Net; Nerve Tissue Proteins; Neural Inhibition; Neurogenesis; Neuropeptide Y; Nitric Oxide Synthase Type I; Patch-Clamp Techniques; Picrotoxin; Pro-Opiomelanocortin; Quinoxalines; Reelin Protein; Serine Endopeptidases; Stem Cell Niche; Synaptic Potentials; Time Factors; Valine

A fundamental property of neuronal networks in Ammon's horn is that each area comprises a single glutamatergic cell population and various types of GABAergic neurons. Here we describe an exception to this rule, in the form of granule cells that reside within the CA3 area and function as glutamatergic nonprincipal cells with distinct properties. CA3 granule cells in normal, healthy rats, similarly to dentate gyrus granule cells, coexpressed calbindin and the homeobox protein Prox1. However, CA3 granule cells were located outside of the dentate gyrus, often hundreds of micrometers from the hilar border, in the lucidum and radiatum layers. CA3 granule cells were present in numbers that were comparable to the rarer GABAergic neuronal subtypes, and their somato-dendritic morphology, intrinsic properties, and perforant path inputs were similar to those of dentate gyrus granule cells. CA3 granule cell axons displayed giant mossy fiber terminals with filopodial extensions, demonstrating that not all mossy fibers originate from the dentate gyrus. Somatic paired recordings revealed that CA3 granule cells innervated CA3 pyramidal and GABAergic cells similarly to conventional mossy fiber synapses. However, CA3 granule cells were distinct in the specific organization of their GABAergic inputs. They received GABAergic synapses from cholecystokinin-expressing mossy fiber-associated cells that did not innervate the dentate granule cell layer, and these synapses demonstrated unusually strong activity-dependent endocannabinoid-mediated inhibition of GABA release. These results indicate that granule cells in the CA3 constitute a glutamatergic, nonprincipal neuronal subtype that is integrated into the CA3 synaptic network.

Topics: Animals; Animals, Newborn; CA3 Region, Hippocampal; Calbindins; Cannabinoid Receptor Modulators; Cholecystokinin; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; gamma-Aminobutyric Acid; Homeodomain Proteins; In Vitro Techniques; Lysine; Membrane Potentials; Microscopy, Electron, Transmission; Nerve Net; Neurons; Neuropeptide Y; Patch-Clamp Techniques; Quinoxalines; Rats; Rats, Wistar; S100 Calcium Binding Protein G; Synapses; Tumor Suppressor Proteins

Although rare, interneurons are pivotal in governing striatal output by extensive axonal arborizations synapsing on medium spiny neurons. Using a genetically modified mouse strain in which a green fluorescent protein (GFP) is driven to be expressed under control of the neuropeptide Y (NPY) promoter, we identified NPY interneurons and compared them with striatal principal neurons. We found that the bacteria artificial chromosome (BAC)-npy mouse expresses GFP with high fidelity in the striatum to the endogenous expression of NPY. Patch-clamp analysis from NPY neurons showed a heterogeneous population of striatal interneurons. In the majority of cells, we observed spontaneous firing of action potentials in extracellular recordings. On membrane rupture, most NPY interneurons could be classified as low-threshold spiking interneurons and had high-input resistance. Voltage-clamp recordings showed that both GABA and glutamate gated ion channels mediate synaptic inputs onto these striatal interneurons. AMPA receptor-mediated spontaneous excitatory postsynaptic currents (sEPSCs) were small in amplitude and infrequent in NPY neurons. Evoked EPSCs did not show short-term plasticity but some rectification. Evoked N-methyl-d-aspartate (NMDA) EPSCs had fast decay kinetics and were poorly sensitive to an NR2B subunit containing NMDA receptor blocker. Spontaneous inhibitory postsynaptic currents (sIPSCs) were mediated by GABA(A) receptors and were quite similar among all striatal neurons studied. On the contrary, evoked IPSCs decayed faster in NPY neurons than in other striatal neurons. These data report for the first time specific properties of synaptic transmission to NPY striatal interneurons.

Topics: Animals; Bicuculline; Biophysical Phenomena; Biophysics; Choline O-Acetyltransferase; Corpus Striatum; Electric Stimulation; Excitatory Amino Acid Antagonists; GABA Antagonists; Green Fluorescent Proteins; Interneurons; Mice; Mice, Transgenic; Neural Inhibition; Neuropeptide Y; Organophosphonates; Parvalbumins; Patch-Clamp Techniques; Piperazines; Quinoxalines; Sodium Channel Blockers; Synapses; Synaptic Potentials; Tetrodotoxin

L-Glutamate, N-methyl-D-aspartate, DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainate increased the release of neuropeptide Y-like immunoreactivity from primary cultures of rat hippocampal neurons incubated in Mg2+(1.2 mM)-containing medium. The neuropeptide Y-like immunoreactivity released by 100 microM glutamate was mainly accounted for by neuropeptide Y (1-36), but consisted in part (about 20%) of peptide YY. The effect of 100 microM glutamate on neuropeptide Y-like immunoreactivity release was largely (about 70%) prevented by the N-methyl-D-aspartate receptor antagonist dizocilpine maleate (10 microM), while the remainder (about 30%) was sensitive to the AMPA/ kainate receptor antagonist 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2-3-dione (10 microM). The AMPA(100 microM)-evoked release of neuropeptide Y-like immunoreactivity was strongly antagonized by 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2-3-dione and by 1-aminophenyl-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine, but it was in part (15-20%) sensitive to dizocilpine. The releases of neuropeptide Y-like immunoreactivity elicited by glutamate, N-methyl-D-aspartate, AMPA and kainate were all strongly Ca(2+)-dependent. Tetrodotoxin (1 microM) abrogated the N-methyl-D-aspartate-evoked release and partly inhibited the release caused by glutamate, but did not modify significantly AMPA- or kainate-evoked release. Removal of Mg2+ from the medium caused increase of neuropeptide Y-like immunoreactivity release, an effect prevented by dizocilpine maleate or 7-Cl-kynurenate. Cyclothiazide (10 microM), a drug known to prevent AMPA receptor desensitization, enhanced the neuropeptide Y-like immunoreactivity release elicited by 100 microM AMPA, but not that caused by 100 microM kainate. However, when used at a lower concentration (50 microM), kainate elicited a response that was potentiated significantly by cyclothiazide. It is concluded that glutamate can stimulate Ca(2+)-dependent release of neuropeptide Y from hippocampal neurons mainly through N-methyl-D-aspartate receptors and, less so, by activating cyclothiazide-sensitive receptors of the AMPA-preferring type.

Topics: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Animals; Anti-Anxiety Agents; Antibody Specificity; Antihypertensive Agents; Benzodiazepines; Benzothiadiazines; Calcium; Cells, Cultured; Chromatography, High Pressure Liquid; Dizocilpine Maleate; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Glutamic Acid; Hippocampus; Kainic Acid; Magnesium; Neurons; Neuropeptide Y; Quinoxalines; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Tetrodotoxin