Synaptic potentials mediated by alpha 7 nicotinic acetylcholine receptors in supraoptic nucleus.
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 GABA(A) 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 alpha7 subunit, but not by dihydro-beta-erythroidine at concentrations known to antagonize alpha4beta2 nAChRs. Although anatomical evidence exists for postsynaptic alpha4beta2 nAChRs in the SON, these results indicate that postsynaptic alpha7 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 alpha7 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 alpha7 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, alpha7 nAChR-mediated EPSPs in hypothalamic neurons.
Hatton
Glenn I
GI
Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521, USA. glenn.hatton@ucr.edu
Yang
Qin Zhao
QZ
D000109:Acetylcholine / Q000494:pharmacology; D000157:Aconitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D021122:Protein Subunits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002800:Cholinesterase Inhibitors; C579165:Chrna7 protein, rat; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D000109:Acetylcholine; D000157:Aconitine