Abstract

Integrate-and-fire (IF) models can provide close matches to the discharge activity of neurons, but do they oversimplify the biophysical properties of the neurons? A single compartment Hodgkin-Huxley (HH) model of the oxytocin neuron has previously been developed, incorporating biophysical measurements of channel properties obtained in vitro. A simpler modified integrate-and-fire model has also been developed, which can match well the characteristic spike patterning of oxytocin neurons as observed in vivo. Here, we extended the HH model to incorporate synaptic input, to enable us to compare spike activity in the model with experimental data obtained in vivo. We refined the HH model parameters to closely match the data, and then matched the same experimental data with a modified IF model, using an evolutionary algorithm to optimise parameter matching. Finally we compared the properties of the modified HH model with those of the IF model to seek an explanation for differences between spike patterning in vitro and in vivo. We show that, with slight modifications, the original HH model, like the IF model, is able to closely match both the interspike interval (ISI) distributions of oxytocin neurons and the observed variability of spike firing rates in vivo and in vitro. This close match of both models to data depends on the presence of a slow activity-dependent hyperpolarisation (AHP); this is represented in both models and the parameters used in the HH model representation match well with optimal parameters of the IF model found by an evolutionary algorithm. The ability of both models to fit data closely also depends on a shorter hyperpolarising after potential (HAP); this is explicitly represented in the IF model, but in the HH model, it emerges from a combination of several components. The critical elements of this combination are identified.

Highlights

  • The supraoptic nucleus of the hypothalamus has been a rich source of insight into how the intrinsic properties of neurons are adapted to meet physiological requirements

  • The chosen recording is from a single supraoptic neuron of an adult virgin female rat anaesthetised with urethane in which the supraoptic nucleus and neural stalk were exposed by ventral surgery and a femoral vein was cannulated for i.v injection of cholecystokinin (CCK)

  • At 9 spikes/s, 17.5% of interspike interval (ISI) are shorter than the mode, and the distribution of ISIs longer than the mode is well fit by a single negative exponential (Fig 1B)

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Summary

Introduction

The supraoptic nucleus of the hypothalamus has been a rich source of insight into how the intrinsic properties of neurons are adapted to meet physiological requirements. Modelling oxytocin neurons nerve terminals in the posterior pituitary gland Some of these neurons make vasopressin, which acts at the kidneys and the peripheral vasculature to mediate antidiuresis and to control plasma volume, the rest make oxytocin, which promotes uterine contractions during parturition and mediates milk let-down in response to suckling. Both oxytocin and vasopressin have additional roles, some mediated by release of oxytocin and vasopressin within the brain, and some by actions at other peripheral targets [1,2]. Oxytocin neurons are osmosensitive: the increases in osmotic pressure result in a graded depolarisation of membrane potential, and, in addition, they receive synaptic input from other osmosensitive neurons in anterior brain regions [10,11]

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