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The Journal of Neuroscience, January 1, 2002, 22(1):29-37

Synaptic Potentials Mediated by alpha 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 alpha -bungarotoxin, antagonists that are selective for nAChRs containing the alpha 7 subunit, but not by dihydro-beta -erythroidine at concentrations known to antagonize alpha 4beta 2 nAChRs. Although anatomical evidence exists for postsynaptic alpha 4beta 2 nAChRs in the SON, these results indicate that postsynaptic alpha 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 alpha 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 alpha 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, alpha 7 nAChR-mediated EPSPs in hypothalamic neurons.

Key words: alpha -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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