Urban I J
Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Utrecht University, The Netherlands.
Prog Brain Res. 1998;119:285-310. doi: 10.1016/s0079-6123(08)61576-9.
The effects of vasopressin (VP), VP fragments and propressophysin glycopeptide on neuronal activities in the septum-hippocampus complex of rats were studied in vitro and in vivo. The frequency of the hippocampus theta rhythm in Brattleboro rats homozygous for diabetes insipidus was significantly slower than that of heterozygous litter mates and normal rats. Intracerebroventricular micro-injection of des-glycine-amide vasopressin corrected for several hours the frequency deficit of the theta rhythm in the homozygous Brattleboro rats and the centrally administered VP slowed down theta rhythm in normal rats. Microinotophoretically administered VP excited single neurons in the lateral septum of ventral hippocampus, and/or facilitated the responses of these neurons to glutamate and to stimulation of the glutamatergic afferent fibers in the fimbria bundle. The excitatory effects of VP vanished within seconds after termination of the peptide administration, however, the peptide-induced enhancement of glutamate and syntatically induced excitations were sustained for up to 60 min after the peptide administration. In vitro, pM concentrations of VP, VP 4-8 and C-terminus glycopeptide of propresophysin facilitated for 30-60 min the glutamate-mediated EPSPs in neurons of the lateral septum or the ventral hippocampus. The EPSPs increase in the lateral septum neurons was not prevented by pretreatment with antagonist of the V1a type of the vasopressin receptor. The resting membrane potential and input resistance were not affected by the peptides. A low-frequency electrical stimulation in the diagonal Band of Broca or in the Bed nucleus of the stria terminals, sources of the vasopressinergic innervation of the septum, facilitated the negative wave of the filed potentials responses evoked in the lateral septum by stimulating the fimbria bundle fibers in control Long-Evans and Brattleboro rats heterozygous for diabetes insipidus. The field potential increase was sustained for several hours after the stimulation, and it was not occluded by long-term potentiation elicited by high frequency stimulation of the fimbria bundle afferent fibers. Brattleboro rats homozygous for diabetes insipidus failed to show the filed potential increase after the diagonal band stimulation. It is suggested that the long-lasting facilitation of glutamate-mediated excitations might be a physiological action of the propressophysin-derived peptides in the septum-hippocampus complex which, in concert with other forms of synaptic plasticity like the long-term potentiation, facilitates the hippocampus-mediated forms of learning and memory. This action is presumably related to the memory enhancing effect of the propressophysin-derived peptides.
在体外和体内研究了血管加压素（VP）、VP片段和促加压素原糖肽对大鼠隔区-海马复合体神经元活动的影响。纯合子遗传性尿崩症的Brattleboro大鼠海马θ节律的频率显著慢于杂合子同窝仔鼠和正常大鼠。脑室内微量注射去甘氨酰胺血管加压素可在数小时内纠正纯合子Brattleboro大鼠θ节律的频率缺陷，而中枢给予VP会使正常大鼠的θ节律减慢。微量电泳给予的VP可兴奋腹侧海马外侧隔区的单个神经元，和/或增强这些神经元对谷氨酸以及对穹窿束中谷氨酸能传入纤维刺激的反应。然而，在肽给药终止后数秒内，VP的兴奋作用消失，而肽诱导的谷氨酸增强作用和句法诱导的兴奋作用在肽给药后可持续长达60分钟。在体外，皮摩尔浓度的VP、VP 4-8和促加压素原的C端糖肽可在30-60分钟内促进外侧隔区或腹侧海马神经元中谷氨酸介导的兴奋性突触后电位（EPSP）。V1a型血管加压素受体拮抗剂预处理并不能阻止外侧隔区神经元中EPSP的增加。肽对静息膜电位和输入电阻没有影响。在隔区血管加压素能神经支配的来源，即布罗卡斜角带或终纹床核进行低频电刺激，可促进对照Long-Evans大鼠和遗传性尿崩症杂合子Brattleboro大鼠中通过刺激穹窿束纤维在外侧隔区诱发的场电位反应的负波。刺激后，场电位增加可持续数小时，并且不会被穹窿束传入纤维高频刺激诱发的长时程增强所掩盖。纯合子遗传性尿崩症的Brattleboro大鼠在斜角带刺激后未出现场电位增加。提示促加压素原衍生肽对谷氨酸介导的兴奋的长期促进作用可能是其在隔区-海马复合体中的一种生理作用，该作用与长时程增强等其他形式的突触可塑性协同作用，促进海马介导的学习和记忆形式。这种作用可能与促加压素原衍生肽的记忆增强作用有关。
