Abstract
Nicotinic acetylcholine receptors containing alpha7 subunits occupy pre- and postsynaptic sites in the adult hippocampus. We find that embryonic hippocampal slices in culture display the receptors most prominently on interneurons where they form clusters localized in part on filopodia. The receptors often co-distribute specifically with GABAA receptors. In septal-hippocampal co-cultures, the filopodia become co-innervated by cholinergic and GABAergic terminals abutting the receptor clusters. Nicotinic transmission appears to stabilize the cholinergic contacts: pharmacological blockade of the alpha7-containing nicotinic receptors increases the rate of filopodia movement and decreases the incidence of the clusters being adjacent to cholinergic terminals. Immunostaining fresh hippocampal slices from neonatal rat pups confirms that cholinergic and GABAergic terminals contact alpha7-containing nicotinic receptor clusters in vivo, and the clusters appear to include filopodial sites. The results indicate a convergence of nicotinic and GABAergic input at specific sites on developing hippocampal interneurons and suggest that synaptic activity helps stabilize the nicotinic contribution.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / metabolism
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Animals
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Animals, Newborn
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Cholinergic Fibers / drug effects
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Cholinergic Fibers / metabolism
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Coculture Techniques
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Dendritic Spines / drug effects
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Dendritic Spines / metabolism
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Dendritic Spines / ultrastructure
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GABA Antagonists / pharmacology
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Hippocampus / cytology
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Hippocampus / embryology*
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Hippocampus / growth & development
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Interneurons / cytology
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Interneurons / drug effects
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Interneurons / metabolism*
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Nicotinic Antagonists / pharmacology
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Organ Culture Techniques
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / metabolism
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Pseudopodia / drug effects
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Pseudopodia / metabolism*
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Pseudopodia / ultrastructure
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Rats
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Rats, Sprague-Dawley
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Receptor Cross-Talk / drug effects
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Receptor Cross-Talk / physiology
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Receptors, GABA-A / drug effects
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Receptors, GABA-A / metabolism*
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Receptors, Nicotinic / drug effects
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Receptors, Nicotinic / metabolism*
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Synapses / drug effects
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Synapses / metabolism*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
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alpha7 Nicotinic Acetylcholine Receptor
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gamma-Aminobutyric Acid / metabolism
Substances
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Chrna7 protein, rat
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GABA Antagonists
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Nicotinic Antagonists
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Receptors, GABA-A
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Receptors, Nicotinic
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alpha7 Nicotinic Acetylcholine Receptor
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gamma-Aminobutyric Acid
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Acetylcholine