title: Responses of magnocellular neurons to osmotic stimulation involves coactivation of excitatory and inhibitory input: an experimental and theoretical analysis.
abstract: How does a neuron, challenged by an increase in synaptic input, display a response that is independent of the initial level of activity? Here we show that both oxytocin and vasopressin cells in the supraoptic nucleus of normal rats respond to intravenous infusions of hypertonic saline with gradual, linear increases in discharge rate. In hyponatremic rats, oxytocin and vasopressin cells also responded linearly to intravenous infusions of hypertonic saline but with much lower slopes. The linearity of response was surprising, given both the expected nonlinearity of neuronal behavior and the nonlinearity of the oxytocin secretory response to such infusions. We show that a simple computational model can reproduce these responses well, but only if it is assumed that hypertonic infusions coactivate excitatory and inhibitory synaptic inputs. This hypothesis was tested first by applying the GABA(A) antagonist bicuculline to the dendritic zone of the supraoptic nucleus by microdialysis. During local blockade of GABA inputs, the response of oxytocin cells to hypertonic infusion was greatly enhanced. We then went on to directly measure GABA release in the supraoptic nucleus during hypertonic infusion, confirming the predicted rise. Together, the results suggest that hypertonic infusions lead to coactivation of excitatory and inhibitory inputs and that this coactivation may confer appropriate characteristics on the output behavior of oxytocin cells. The nonlinearity of oxytocin secretion that accompanies the linear increase in oxytocin cell firing rate reflects frequency-facilitation of stimulus-secretion coupling at the neurohypophysis.
authors.affiliation: Department of Biomedical Sciences, University Medical School, Edinburgh EH8 9XD, United Kingdom. gareth.leng@ed.ac.uk
authors.forename: G
authors.initials: G
authors.lastname: Leng
authors.forename: C H
authors.initials: CH
authors.lastname: Brown
authors.forename: P M
authors.initials: PM
authors.lastname: Bull
authors.forename: D
authors.initials: D
authors.lastname: Brown
authors.forename: S
authors.initials: S
authors.lastname: Scullion
authors.forename: J
authors.initials: J
authors.lastname: Currie
authors.forename: R E
authors.initials: RE
authors.lastname: Blackburn-Munro
authors.forename: J
authors.initials: J
authors.lastname: Feng
authors.forename: T
authors.initials: T
authors.lastname: Onaka
authors.forename: J G
authors.initials: JG
authors.lastname: Verbalis
authors.forename: J A
authors.initials: JA
authors.lastname: Russell
authors.forename: M
authors.initials: M
authors.lastname: Ludwig
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage; D003198:Computer Simulation; D003894:Deamino Arginine Vasopressin; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000008:administration & dosage; D007010:Hyponatremia / Q000097:blood / Q000139:chemically induced; D007262:Infusions, Intravenous; D008297:Male; D017551:Microdialysis; D008959:Models, Neurological; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D009994:Osmolar Concentration; D010121:Oxytocin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage; D012964:Sodium / Q000097:blood; D013268:Stimulation, Chemical; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D014667:Vasopressins / Q000819:agonists / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018756:GABA Antagonists; D012462:Saline Solution, Hypertonic; D014667:Vasopressins; D010121:Oxytocin; D005680:gamma-Aminobutyric Acid; D012964:Sodium; D003894:Deamino Arginine Vasopressin; D001640:Bicuculline