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The Journal of Neuroscience, January 1, 2002, 22(1):29-37
Synaptic Potentials Mediated by 7 Nicotinic Acetylcholine
Receptors in Supraoptic Nucleus
Glenn I.
Hatton and
Qin Zhao
Yang
Department of Cell Biology and Neuroscience, University of
California, Riverside, California 92521
Brain slice preparations preserving projections from nearby
forebrain cholinergic neurons to the supraoptic nucleus (SON) were used
to study synaptic potentials mediated by nicotinic acetylcholine receptors (nAChRs) in the hypothalamus. Paired-pulse electrical stimulation in an area anterior to the SON that was rich in cholinergic cells confirmed the monosynaptic nature of the connections to putative oxytocin and vasopressin SON neurons. With ionotropic glutamate and GABAA transmission blocked, this stimulation
evoked fast, atropine-insensitive EPSPs that were sensitive to nAChR antagonists. Evoked EPSPs were blocked by methyllycaconitine and -bungarotoxin, antagonists that are selective for nAChRs containing the 7 subunit, but not by dihydro- -erythroidine at concentrations known to antagonize 4 2 nAChRs. Although anatomical evidence exists for postsynaptic 4 2 nAChRs in the SON, these results indicate that postsynaptic 7 nAChRs are primarily responsible for
the cholinergically mediated EPSPs. Repetitive stimulation suggested
partial desensitization of the receptors. With ionotropic glutamate
transmission blocked, inhibition of AChE increased spontaneous EPSP
frequency and amplitude, suggesting spontaneous ACh release. ACh,
nicotine, and choline (a selective 7 nAChR agonist) were effective
in evoking action potentials and repetitive firing with synaptic
transmission blocked by low Ca2+, high
Mg2+ medium. These agonists were also effective in
evoking the type of phasic bursts characteristic of vasopressin
neurons, long thought to be completely dependent on activation of NMDA
receptors (NMDARs). Because phasic bursting is
Ca2+-dependent, the functional equivalence of 7
nAChR and NMDAR activation in this regard is likely attributable to
their large Ca2+ fluxing capacities. This is the
first demonstration that synaptically released ACh results in fast,
7 nAChR-mediated EPSPs in hypothalamic neurons.
Key words:
-bungarotoxin; choline; intracellular recording; magnocellular neuroendocrine neurons; methyllycaconitine; nicotine
Copyright © 2002 Society for Neuroscience 0270-6474/02/22129-09$05.00/0
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