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The Journal of Neuroscience, October 15, 2001, 21(20):7993-8003

Ultrastructural Distribution of the alpha 7 Nicotinic Acetylcholine Receptor Subunit in Rat Hippocampus

Ruth Fabian-Fine1, 2, Paul Skehel2, Mick L. Errington2, Heather A. Davies1, Emanuele Sher3, Michael G. Stewart1, and Alan Fine2, 4

1 Department of Biological Sciences, The Open University, Milton Keynes, MK7 6AA, United Kingdom, 2 Division of Neurophysiology, National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom, 3 Lilly Research Centre, Eli Lilly and Co., Erl Wood Manor, Windlesham, Surrey GU20 6PH, United Kingdom, and 4 Department of Physiology and Biophysics, Dalhousie University Faculty of Medicine, Halifax, Nova Scotia B3H 4H7, Canada

Acetylcholine (ACh) is an important neurotransmitter in the mammalian brain; it is implicated in arousal, learning, and other cognitive functions. Recent studies indicate that nicotinic receptors contribute to these cholinergic effects, in addition to the established role of muscarinic receptors. In the hippocampus, where cholinergic involvement in learning and memory is particularly well documented, alpha 7 nicotinic acetylcholine receptor subunits (alpha 7 nAChRs) are highly expressed, but their precise ultrastructural localization has not been determined. Here, we describe the results of immunogold labeling of serial ultrathin sections through stratum radiatum of area CA1 in the rat. Using both anti-alpha 7 nAChR immunolabeling and alpha -bungarotoxin binding, we find that alpha 7 nAChRs are present at nearly all synapses in CA1 stratum radiatum, with immunolabeling present at both presynaptic and postsynaptic elements. Morphological considerations and double immunolabeling indicate that GABAergic as well as glutamatergic synapses bear alpha 7 nAChRs, at densities approaching those observed for glutamate receptors in CA1 stratum radiatum. Postsynaptically, alpha 7 nAChRs often are distributed at dendritic spines in a perisynaptic annulus. In the postsynaptic cytoplasm, immunolabeling is associated with spine apparatus and other membranous structures, suggesting that alpha 7 nAChRs may undergo dynamic regulation, with insertion into the synapse and subsequent internalization. The widespread and substantial expression of alpha 7 nAChRs at synapses in the hippocampus is consistent with an important role in mediating and/or modulating synaptic transmission, plasticity, and neurodegeneration.

Key words: acetylcholine receptors; nicotine; dendritic spines; postsynaptic density; immuno-electron microscopy; glutamate; GABA; Abeta 1-42


Copyright © 2001 Society for Neuroscience  0270-6474/01/21207993-11$05.00/0


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