title: Phasic bursts in rat magnocellular neurosecretory cells are not intrinsically regenerative in vivo.
abstract: Vasopressinergic hypothalamic magnocellular neurosecretory cells fire in phasic bursts. Burst initiation involves summation of postsynaptic potentials to generate action potentials. Action potentials are each followed by a nonsynaptic depolarizing after-potential that summates temporally to generate a plateau potential and so sustain activity throughout the burst. It is unknown whether this plateau potential exceeds spike threshold in vivo to cause intrinsic regenerative firing or simply approaches threshold to increase the probability that excitatory postsynaptic potentials will trigger further action potentials. Here we show that pharmacological blockade of ionotropic glutamatergic transmission by microdialysis application of kynurenic acid into the supraoptic nucleus of anaesthetized rats prevents spontaneous bursts and bursts (after-discharge) evoked by short trains of antidromically stimulated action potentials in magnocellular neurosecretory cells. Even during prolonged depolarization induced by 1 m NaCl infusion, kynurenic acid microdialysis application still blocked after-discharge. The ability of kynurenic acid to block after-discharge during osmotic stimulation was not caused by an unmasking of inhibitory postsynaptic potentials as kynurenic acid was equally effective in the presence of the ionotropic gamma-aminobutyric acid receptor antagonist, bicuculline, nor did it result from inhibition of plateau potential amplitude as this was unaffected by kynurenic acid and bicuculline in vitro, as was after-discharge evoked in vitro. We conclude that phasic bursts are nonregenerative in vivo but rather require continued excitatory synaptic input activity superimposed upon a subthreshold plateau potential to sustain burst activity.
authors.affiliation: School of Biomedical and Clinical Laboratory Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, Scotland, UK. Colin.Brown@ed.ac.uk
authors.forename: Colin H
authors.initials: CH
authors.lastname: Brown
authors.forename: Philip M
authors.initials: PM
authors.lastname: Bull
authors.forename: Charles W
authors.initials: CW
authors.lastname: Bourque
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007478:Iontophoresis / Q000379:methods; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D013495:Supraoptic Nucleus / Q000166:cytology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D012462:Saline Solution, Hypertonic; D007736:Kynurenic Acid; D001640:Bicuculline