title: GABAergic excitation promotes neuronal differentiation in adult hippocampal progenitor cells.
abstract: Hippocampal activity influences neurogenesis in the adult dentate gyrus; however, little is known about the involvement of the hippocampal circuitry in this process. In the subgranular zone of the adult dentate gyrus, neurogenesis involves a series of differentiation steps from radial glia-like stem/progenitor (type-1) cells, to transiently amplifying neuronal progenitor (type-2) cells, to postmitotic neurons. In this study, we conducted GFP-targeted recordings of progenitor cells in fresh hippocampal slices from nestin-GFP mice and found that neuronal progenitor (type-2) cells receive active direct neural inputs from the hippocampal circuitry. This input was GABAergic but not glutamatergic. The GABAergic inputs depolarized type-2 cells because of their elevated [Cl(-)](i). This excitation initiated an increase of [Ca(2+)](i) and the expression of NeuroD. A BrdU-pulse labeling study with GABA(A)-R agonists demonstrated the promotion of neuronal differentiation via this GABAergic excitation. Thus, it appears that GABAergic inputs to hippocampal progenitor cells promote activity-dependent neuronal differentiation.
authors.affiliation: Department of Integrated Biosciences, University of Tokyo, Kashiwa 277-8562, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tozuka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuda
authors.forename: Takashi
authors.initials: T
authors.lastname: Namba
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Seki
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Hisatsune
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001640:Bicuculline / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000378:metabolism; D064026:Calbindins; D002118:Calcium / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006624:Hippocampus / Q000166:cytology*; D049690:History, Ancient; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007381:Intermediate Filament Proteins / Q000235:genetics; D019394:Ki-67 Antigen / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron / Q000379:methods; D016202:N-Methylaspartate / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2; D013234:Stem Cells / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D015761:4-Aminopyridine; D051792:Basic Helix-Loop-Helix Proteins; D001640:Bicuculline; D001973:Bromodeoxyuridine; D064026:Calbindins; D002118:Calcium; D018690:Excitatory Amino Acid Agonists; D018756:GABA Antagonists; D005998:Glycine; D049452:Green Fluorescent Proteins; D007381:Intermediate Filament Proteins; D019394:Ki-67 Antigen; D016202:N-Methylaspartate; D009419:Nerve Tissue Proteins; D064231:Nestin; D039842:Neural Cell Adhesion Molecule L1; D009532:Nickel; D010751:Phosphopyruvate Hydratase; D026902:Potassium Channel Blockers; D064030:S100 Calcium Binding Protein G; D012794:Sialic Acids; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D013779:Tetrodotoxin; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D005680:gamma-Aminobutyric Acid; C577485:Nes protein, mouse; C578878:Slc12a2 protein, mouse; C492244:Viaat protein, mouse; C103469:polysialyl neural cell adhesion molecule; C093564:Neurogenic differentiation factor 1