Pulsatile oxytocin secretion into the blood is important for inducing uterine contractions during birth. Magnocellular oxytocin neurones become activated during parturition, exhibiting increased firing rate with superimposed synchronised burst firing that generates the pulses of oxytocin secretion (Summerlee 1989). However, in parturition the underlying mechanisms of activation of oxytocin neurones are not well understood. We have used an anaesthetised rat model to investigate oxytocin neurone activity during birth. Administration of oxytocin pulses i.v. at term pregnancy enhances strong uterine contractions and, as in conscious rats, induces the birth of pups. This triggers enhanced magnocellular oxytocin neurone activation, including increased firing rate and Fos expression. Possible mechanisms that underlie this activation include activation of the nucleus of the tractus solitarius (NTS) noradrenergic pathway, which relays uterine signals to the hypothalamus. NTS neurones that project to the supraoptic nucleus (SON) and that express tyrosine hydroxylase (rate limiting enzyme in noradrenaline synthesis pathway) become activated during parturition. Uterine contraction causes intermittent noradrenaline release within the SON (Douglas et al 2001), and infusion of alpha1-adrenergic antagonist into the SON prevents the uterine-contraction induced Fos expression. Also, alpha1-adrenergic agonist, phenylephrine, given centrally greatly accelerates the speed of birth of pups during spontaneous parturition. Since phenylephrine facilitates burst firing of oxytocin neurones in vitro (Wang and Hatton 2004), we hypothesise a role for brainstem noradrenergic neurones in the generation of oxytocin neurone bursting activity. Therefore, co-ordinated uterine and brain mechanisms at term pregnancy generate a positive feedback loop which precipitates birth.

Supported by The Wellcome Trust