Ingram C D, Ciobanu R, Coculescu I L, Tanasescu R, Coculescu M, Mihai R
Department of Anatomy, University of Bristol, UK.
Prog Brain Res. 1998;119:351-64. doi: 10.1016/s0079-6123(08)61580-0.
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.
血管加压素（VP）是视交叉上核（SCN）中的主要递质之一。SCN背内侧区约20%的神经元合成该肽，并且SCN中很大比例（>40%）的神经元会被通过V1受体起作用的VP所兴奋。这表明VP可能作为该核团内电活动的反馈调节因子。通过用V1拮抗剂进行灌流可以证明这种内在的兴奋性信号，该拮抗剂会降低自发神经活动。由于VP的合成和释放以昼夜节律的方式发生，这会导致可变的反馈兴奋，这可能有助于神经时钟活动的昼夜节律模式。缺乏VP的动物行为节律的昼夜振幅降低（例如运动和皮层脑电图节律），这一观察结果支持了VP在放大节律性方面的这一作用。随着年龄增长，VP表达下降，尽管老年动物中被VP兴奋的SCN神经元比例没有变化，但自发电活动的节律却逐渐下降，这与内源性兴奋性反馈降低一致。然而，完全缺乏任何VP表达的纯合布拉特洛维大鼠仍能维持电活动节律，这表明VP不是产生昼夜活动的唯一因素。这种节律性的产生可能取决于VP与其他递质系统的相互作用，例如抑制性递质生长抑素和γ-氨基丁酸，它们的功效表现出昼夜变化。除了在电活动内源性节律的反馈放大中发挥作用外，VP还作为传出信号的一部分作用于中枢神经系统的其他部分，在那里它可能调节许多行为和生理节律，包括下丘脑-垂体-肾上腺轴的昼夜活动。因此，VP兼具放大和信号传递功能，使其成为哺乳动物神经元时钟功能的重要组成部分。
