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The Journal of Neuroscience, June 15, 2002, 22(12):5001-5015
7 Nicotinic Acetylcholine Receptors Occur at Postsynaptic
Densities of AMPA Receptor-Positive and -Negative Excitatory Synapses
in Rat Sensory Cortex
Robert B.
Levy and
Chiye
Aoki
New York University Center for Neural Science, New York, New York
10003
NMDA receptor (NMDAR) activation requires concurrent
membrane depolarization, and glutamatergic synapses lacking AMPA
receptors (AMPARs) are often considered "silent" in the
absence of another source of membrane depolarization. During the second
postnatal week, NMDA currents can be enhanced in rat auditory cortex
through activation of the 7 nicotinic acetylcholine receptor
( 7nAChR). Electrophysiological results support a mainly presynaptic
role for 7nAChR at these synapses. However, immunocytochemical
evidence that 7nAChR is prevalent at postsynaptic sites of
glutamatergic synapses in hippocampus and neocortex, along with
emerging electrophysiological evidence for postsynaptic nicotinic
currents in neocortex and hippocampus, has prompted speculation that
7nAChR allows for activation of NMDAR postsynaptically at synapses
lacking AMPAR. Here we used dual immunolabeling and electron microscopy
to examine the distribution of 7nAChR relative to AMPAR (GluR1,
GluR2, and GluR3 subunits combined) at excitatory synapses in
somatosensory cortex of adult and 1-week-old rats. 7nAChR occurred
discretely over most of the thick postsynaptic densities in all
cortical layers of both age groups. AMPAR immunoreactivity was also
detectable at most synapses; its distribution was independent of that
of 7nAChR. In both age groups, approximately one-quarter of
asymmetrical synapses were 7nAChR positive and AMPAR negative. The
variability of postsynaptic 7nAChR labeling density was greater at
postnatal day (PD) 7 than in adulthood, and PD 7 neuropil contained a
subset of small AMPA receptor-negative synapses with a high density of 7nAChR immunoreactivity. These observations support the idea that
acetylcholine receptors can aid in activating glutamatergic synapses
and work together with AMPA receptors to mediate postsynaptic excitation throughout life.
Key words:
sensory cortex; receptive field properties; 7
nicotinic acetylcholine receptor; glutamate; AMPA receptor; NMDA
receptor; synaptic plasticity; early postnatal development; postsynaptic density; immunocytochemistry; electron microscopy
Copyright © 2002 Society for Neuroscience 0270-6474/02/22125001-15$05.00/0
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