Maícas Royo J, Brown C H, Leng G, MacGregor D J
Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK.
Centre for Neuroendocrinology and Department of Physiology, University of Otago, Otago, New Zealand.
J Neuroendocrinol. 2016 Apr;28(4):n/a. doi: 10.1111/jne.12358.
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.
大鼠视上核的催产素神经元对渗透压有反应，在其他条件相同的情况下，它们的平均放电频率与血浆钠浓度成正比。然而，单个动作电位的时间受高度随机事件的支配，即兴奋性突触输入的随机发生，细胞外渗透压升高会增加其发生的概率。因此，峰间期（ISI）非常不规则。在本研究中，我们通过对催产素神经元放电模式的统计分析表明，以几秒的时间间隔测量的平均放电频率比根据ISI的变异性预期的更为规则。这与一种内在的活动依赖性负反馈机制一致。为了验证这一点，我们将观察到的神经元放电模式与一个漏电整合发放模型神经元产生的放电模式进行了比较，该模型经过修改以表现出已知存在于催产素神经元中的活动依赖性机制。延长的超极化后电位（AHP）的存在对于模拟观察到的平均放电频率的规则化能力至关重要，尽管我们还必须在模型中添加一个去极化后电位（DAP；有时称为去极化后电位）以匹配观察到的ISI分布。我们通过将该模型的行为与暴露于蜂毒明肽（一种中等AHP的阻滞剂）的催产素神经元的行为进行比较来测试该模型。良好的拟合表明，中等AHP在非爆发性活动期间积极参与催产素神经元的放电模式，并且催产素神经元通常表达DAP，尽管这通常被更大的AHP叠加所掩盖。
