title: Oxytocin Neurones: Intrinsic Mechanisms Governing the Regularity of Spiking Activity.
abstract: Oxytocin neurones of the rat supraoptic nucleus are osmoresponsive and, with all other things being equal, they fire at a mean rate that is proportional to the plasma sodium concentration. However, individual spike times are governed by highly stochastic events, namely the random occurrences of excitatory synaptic inputs, the probability of which is increased by increasing extracellular osmotic pressure. Accordingly, interspike intervals (ISIs) are very irregular. In the present study, we show, by statistical analyses of firing patterns in oxytocin neurones, that the mean firing rate as measured in bins of a few seconds is more regular than expected from the variability of ISIs. This is consistent with an intrinsic activity-dependent negative-feedback mechanism. To test this, we compared observed neuronal firing patterns with firing patterns generated by a leaky integrate-and-fire model neurone, modified to exhibit activity-dependent mechanisms known to be present in oxytocin neurones. The presence of a prolonged afterhyperpolarisation (AHP) was critical for the ability to mimic the observed regularisation of mean firing rate, although we also had to add a depolarising afterpotential (DAP; sometimes called an afterdepolarisation) to the model to match the observed ISI distributions. We tested this model by comparing its behaviour with the behaviour of oxytocin neurones exposed to apamin, a blocker of the medium AHP. Good fits indicate that the medium AHP actively contributes to the firing patterns of oxytocin neurones during non-bursting activity, and that oxytocin neurones generally express a DAP, even though this is usually masked by superposition of a larger AHP.
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK.
authors.forename: J
authors.initials: J
authors.lastname: Maícas Royo
authors.affiliation: Centre for Neuroendocrinology and Department of Physiology, University of Otago, Otago, New Zealand.
authors.forename: C H
authors.initials: CH
authors.lastname: Brown
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK.
authors.forename: G
authors.initials: G
authors.lastname: Leng
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: MacGregor
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009997:Osmotic Pressure / Q000502:physiology; D010121:Oxytocin / Q000502:physiology*; D051381:Rats; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology
chemical_list: D001030:Apamin; D010121:Oxytocin
keywords: computational modelling; electrophysiology; oxytocin; supraoptic nucleus