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bioRxiv · 10.1101/2021.06.01.446490

Plasticity in intrinsic excitability of hypothalamic magnocellular neurosecretory neurons in late-pregnant and lactating rats

Perkinson, M. R.·Augustine, R. A.·Bouwer, G. T.·Brown, E. F.·Cheong, I.·Seymour, A. J.·Fronius, M.·Brown, C. H.
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Abstract

Oxytocin and vasopressin secretion from the posterior pituitary gland are required for normal pregnancy and lactation. Oxytocin secretion is relatively low and constant under basal conditions but becomes pulsatile during birth and lactation to stimulate episodic contraction of the uterus for delivery of the fetus and milk ejection during suckling. Vasopressin secretion is maintained in pregnancy and lactation despite reduced osmolality (the principal stimulus for vasopressin secretion) to increase water retention to cope with the cardiovascular demands of pregnancy and lactation. Oxytocin and vasopressin secretion are determined by the action potential (spike) firing of magnocellular neurosecretory neurons of the hypothalamic supraoptic and paraventricular nucleus. In addition to synaptic input activity, spike firing depends on intrinsic excitability conferred by the suite of channels expressed by the neurons. Therefore, we analysed oxytocin and vasopressin neuron activity in anaesthetised non-pregnant, late-pregnant and lactating rats to test the hypothesis that intrinsic excitability of oxytocin and vasopressin neurons is increased in late pregnancy and lactation to promote oxytocin and vasopressin secretion required for successful pregnancy and lactation. Hazard analysis of spike firing revealed a higher incidence of post-spike hyperexcitability immediately following each spike in oxytocin neurons, but not in vasopressin neurons, in late pregnancy and lactation, which is expected to facilitate high frequency firing during bursts. Despite lower osmolality in late-pregnant and lactating rats, vasopressin neuron activity was not different between non-pregnant, late-pregnant and lactating rats, and blockade of osmosensitive {Delta}N-TRPV1 channels inhibited vasopressin neurons to a similar extent in non-pregnant, late-pregnant and lactating rats. Furthermore, supraoptic nucleus {Delta}N-TRPV1 mRNA expression was not different between non-pregnant and late-pregnant rats, suggesting that enhanced activity of {Delta}N-TRPV1 channels might maintain vasopressin neuron activity to increase water retention during pregnancy and lactation.

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Perkinson, M. R., Augustine, R. A., Bouwer, G. T., Brown, E. F., Cheong, I., Seymour, A. J., Fronius, M., Brown, C. H.. 2021-06-02. Plasticity in intrinsic excitability of hypothalamic magnocellular neurosecretory neurons in late-pregnant and lactating rats. https://doi.org/10.1101/2021.06.01.446490

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