GABAergic excitation promotes neuronal differentiation in adult hippocampal progenitor cells

Neuron. 2005 Sep 15;47(6):803-15. doi: 10.1016/j.neuron.2005.08.023.

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.

Publication types

  • Historical Article

MeSH terms

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

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Calbindins
  • Excitatory Amino Acid Agonists
  • GABA Antagonists
  • Intermediate Filament Proteins
  • Ki-67 Antigen
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Neural Cell Adhesion Molecule L1
  • Potassium Channel Blockers
  • S100 Calcium Binding Protein G
  • Sialic Acids
  • Slc12a2 protein, mouse
  • Sodium-Potassium-Chloride Symporters
  • Solute Carrier Family 12, Member 2
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • Viaat protein, mouse
  • polysialyl neural cell adhesion molecule
  • Green Fluorescent Proteins
  • NeuroD protein
  • Tetrodotoxin
  • gamma-Aminobutyric Acid
  • N-Methylaspartate
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Nickel
  • 4-Aminopyridine
  • Phosphopyruvate Hydratase
  • Bromodeoxyuridine
  • Calcium
  • Glycine
  • Bicuculline