Abstract
In the postnatal subventricular zone (SVZ), local cues or signaling molecules released from neuroblasts limit the proliferation of glial fibrillary acidic protein (GFAP)-expressing progenitors thought to be stem cells. However, signals between SVZ cells have not been identified. We show that depolarization of neuroblasts induces nonsynaptic SNARE-independent GABA(A) receptor currents in GFAP-expressing cells, the time course of which depends on GABA uptake in acute mouse slices. We found that GABA(A) receptors are tonically activated in GFAP-expressing cells, consistent with the presence of spontaneous depolarizations in neuroblasts that are sufficient to induce GABA release. These data demonstrate the existence of nonsynaptic GABAergic signaling between neuroblasts and GFAP-expressing cells. Furthermore, we show that GABA(A) receptor activation in GFAP-expressing cells limits their progression through the cell cycle. Thus, as GFAP-expressing cells generate neuroblasts, GABA released from neuroblasts provides a feedback mechanism to control the proliferation of GFAP-expressing progenitors by activating GABA(A) receptors.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Newborn
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Botulinum Toxins
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Bromodeoxyuridine / metabolism
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Cadmium / pharmacology
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Cell Count / methods
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Cell Proliferation*
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Chelating Agents / pharmacology
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Cyclooxygenase Inhibitors / pharmacology
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Dose-Response Relationship, Drug
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Dose-Response Relationship, Radiation
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Drug Interactions
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / pharmacology
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Electric Stimulation / methods
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Enzyme Inhibitors / pharmacology
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GABA Antagonists / pharmacology
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Gene Expression Regulation / drug effects
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Glial Fibrillary Acidic Protein / genetics
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Glial Fibrillary Acidic Protein / metabolism*
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Green Fluorescent Proteins / biosynthesis
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Immunohistochemistry / methods
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In Vitro Techniques
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Lateral Ventricles / cytology*
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Meclofenamic Acid / pharmacology
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Membrane Potentials / drug effects
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Membrane Potentials / genetics
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Mice
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Mice, Transgenic
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Neurons / cytology
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Neurons / drug effects
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Neurons / physiology*
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Nickel / pharmacology
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Patch-Clamp Techniques / methods
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Potassium / pharmacology
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Sodium Channel Blockers / pharmacology
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Spider Venoms / pharmacology
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Stem Cells / physiology*
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Tetrodotoxin / pharmacology
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gamma-Aminobutyric Acid / metabolism*
Substances
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Chelating Agents
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Cyclooxygenase Inhibitors
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Enzyme Inhibitors
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GABA Antagonists
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Glial Fibrillary Acidic Protein
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Sodium Channel Blockers
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Spider Venoms
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Cadmium
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1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
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Green Fluorescent Proteins
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Tetrodotoxin
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Meclofenamic Acid
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Egtazic Acid
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gamma-Aminobutyric Acid
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alpha-latrotoxin
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Nickel
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Botulinum Toxins
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Bromodeoxyuridine
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Potassium