Oxytocin neurones: intrinsic mechanisms governing the regularity of spiking activity

Oxytocin neurones of the rat supraoptic nucleus are osmoresponsive, and, 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 - the random occurrences of excitatory synaptic inputs, the probability of which are increased by increasing extracellular osmotic pressure, and, accordingly, interspike intervals (ISIs) are very irregular. However, we show here 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, but we also had to add a depolarising afterpotential (DAP; sometimes called an afterdepolarisation) to the model to also match the observed ISI distributions. We tested this model by comparing its behaviour to 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 at rest, and that oxytocin neurones generally express a DAP, even though it is usually masked by superposition of a larger AHP. This article is protected by copyright. All rights reserved.