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The Journal of Neuroscience, October 15, 2001, 21(20):7993-8003
Ultrastructural Distribution of the 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, 7 nicotinic acetylcholine receptor subunits ( 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- 7 nAChR immunolabeling and -bungarotoxin
binding, we find that 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 7 nAChRs, at densities approaching those observed for
glutamate receptors in CA1 stratum radiatum. Postsynaptically, 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
7 nAChRs may undergo dynamic regulation, with insertion into the
synapse and subsequent internalization. The widespread and substantial
expression of 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; A 1-42
Copyright © 2001 Society for Neuroscience 0270-6474/01/21207993-11$05.00/0
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