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.
MeSH terms
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4-Aminopyridine / pharmacology
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Animals
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Bicuculline / pharmacology
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Bromodeoxyuridine / metabolism
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Calbindins
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Calcium / metabolism
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Cell Count / methods
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Cell Differentiation / drug effects
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Cell Differentiation / physiology*
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Drug Interactions
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Electric Stimulation / methods
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Excitatory Amino Acid Agonists / pharmacology
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GABA Antagonists / pharmacology
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Glycine / pharmacology
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Green Fluorescent Proteins / biosynthesis
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Hippocampus / cytology*
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History, Ancient
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Immunohistochemistry / methods
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In Vitro Techniques
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Intermediate Filament Proteins / genetics
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Ki-67 Antigen / metabolism
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Mice
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Mice, Transgenic
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Microscopy, Immunoelectron / methods
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N-Methylaspartate / pharmacology
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Nestin
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Neural Cell Adhesion Molecule L1 / metabolism
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Neurons / classification
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Neurons / drug effects
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Neurons / metabolism*
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Neurons / ultrastructure
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Nickel / pharmacology
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Patch-Clamp Techniques / methods
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Phosphopyruvate Hydratase / metabolism
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Potassium Channel Blockers / pharmacology
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S100 Calcium Binding Protein G / metabolism
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Sialic Acids / metabolism
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Sodium-Potassium-Chloride Symporters / metabolism
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Solute Carrier Family 12, Member 2
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Stem Cells / drug effects*
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Tetrodotoxin / pharmacology
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Vesicular Inhibitory Amino Acid Transport Proteins / metabolism
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
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gamma-Aminobutyric Acid / metabolism*
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gamma-Aminobutyric Acid / pharmacology
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Calbindins
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Excitatory Amino Acid Agonists
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GABA Antagonists
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Intermediate Filament Proteins
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Ki-67 Antigen
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Nerve Tissue Proteins
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Nes protein, mouse
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Nestin
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Neural Cell Adhesion Molecule L1
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Potassium Channel Blockers
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S100 Calcium Binding Protein G
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Sialic Acids
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Slc12a2 protein, mouse
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Sodium-Potassium-Chloride Symporters
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Solute Carrier Family 12, Member 2
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Vesicular Inhibitory Amino Acid Transport Proteins
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Viaat protein, mouse
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polysialyl neural cell adhesion molecule
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Green Fluorescent Proteins
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Neurogenic differentiation factor 1
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Tetrodotoxin
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gamma-Aminobutyric Acid
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N-Methylaspartate
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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Nickel
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4-Aminopyridine
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Phosphopyruvate Hydratase
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Bromodeoxyuridine
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Calcium
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Glycine
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Bicuculline