Abstract
Recent studies have implicated the classical neurotransmitters GABA and glutamate in the regulation of neural progenitor proliferation. We now show that GABA and glutamate have opposite effects on the two neural progenitor populations in the ventricular zones (VZs) and subventricular zones (SVZs) of the embryonic cerebrum. Application of either molecule to organotypic slice cultures dramatically increases proliferation in the VZ by shortening the cell cycle, whereas proliferation in the SVZ is decreased. These disparate effects, measured both by bromodeoxyuridine uptake and the expansion of retrovirally labeled progenitor clones, are mimicked by the application of specific GABA and glutamate agonists and are blocked by antagonists. Thus, the relative contributions of the VZ and SVZ to neocortical growth may be regulated by differential responsiveness to GABA and glutamate.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
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Animals
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Antimetabolites / pharmacology
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Bromodeoxyuridine / pharmacology
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Cell Differentiation / drug effects
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Cell Differentiation / physiology
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Cell Division / drug effects
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Cell Division / physiology
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Cell Movement / drug effects
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Cell Movement / physiology
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Cerebral Ventricles / chemistry
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Cerebral Ventricles / cytology*
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Cerebral Ventricles / embryology
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Clone Cells / drug effects
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Clone Cells / physiology
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Excitatory Amino Acid Agonists / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Fetus / cytology
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GABA Agonists / pharmacology
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GABA Antagonists / pharmacology
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Glutamic Acid / analysis
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Glutamic Acid / pharmacology*
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Kainic Acid / pharmacology
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Mice
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Mice, Inbred ICR
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Muscimol / pharmacology
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Neocortex / chemistry
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Neocortex / cytology*
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Neocortex / embryology
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Neurons / cytology*
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Organ Culture Techniques
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Stem Cells / cytology*
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Stem Cells / drug effects
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gamma-Aminobutyric Acid / analysis
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gamma-Aminobutyric Acid / pharmacology*
Substances
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Antimetabolites
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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GABA Agonists
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GABA Antagonists
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Muscimol
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Glutamic Acid
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gamma-Aminobutyric Acid
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6-Cyano-7-nitroquinoxaline-2,3-dione
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Bromodeoxyuridine
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Kainic Acid