Vasopressin neurotransmission and the control of circadian rhythms in the suprachiasmatic nucleus.

Vasopressin (VP) is one of the principal transmitters in the suprachiasmatic nucleus (SCN). Approximately 20% of neurones in the dorsomedial division of the SCN synthesize the peptide and a high proportion of SCN neurones (> 40%) are excited by VP acting through the V1 receptor. This suggests that VP may act as a feedback regulator of electrical activity within the nucleus. Such an intrinsic excitatory signal can be demonstrated by perifusion with a V1 antagonist which reduces spontaneous neural activity. As the synthesis and release of VP occurs in a circadian manner, this leads to a variable feedback excitation which may contribute to the circadian pattern of activity of the neural clock. This role in amplifying rhythmicity is supported by observations that animals deficient in VP show a reduced circadian amplitude of behavioural rhythms (e.g. locomotor and cortical electroencephalographic rhythms). VP expression declines during ageing and although aged animals show no change in the proportion of SCN neurones excited by VP, the rhythm of spontaneous electrical activity shows a progressive decline, consistent with the reduced endogenous excitatory feedback. However, the homozygous Brattleboro rat which lacks any VP expression still maintains rhythms of electrical activity, indicating that VP is not the sole factor generating circadian activity. The generation of this rhythmicity may depend upon the interaction of VP with other transmitter systems, such as the inhibitory transmitters somatostatin and GABA which show a circadian variation in efficacy. In addition to its role in feedback amplification of the endogenous rhythm of electrical activity, VP also functions as part of the efferent signal to the rest of the CNS where it potentially regulates a number of behavioural and physiological rhythms, including the circadian activity of the hypothalamo-pituitary-adrenal axis. Thus, the combined amplification and signalling functions makes VP an important component of the neuronal clock function in mammals.