title: Long-lasting enhancement of synaptic excitability of CA1/subiculum neurons of the rat ventral hippocampus by vasopressin and vasopressin(4-8).
abstract: Vasopressin (VP) is axonally distributed in many brain structures, including the ventral hippocampus. Picogram quantities of VP injected into the hippocampus improve the passive avoidance response of rats, presumably by enhancing memory processes. Vasopressin is metabolized by the brain tissue into shorter peptides, such as [pGlu4,Cyt6]VP(4-9) and [pGlu4,Cyt6]VP(4-8), which preserve the behavioral activity but lose the peripheral activities of the parent hormone. Using brain slices, we investigated whether VP or VP(4-8) affects excitatory postsynaptic potentials (EPSPs) and/or membrane responses to depolarization in neurons of the CA1/subiculum of the ventral hippocampus. The EPSPs were evoked by stimulating the striatum radiatum of the CA1 field; the membrane responses were elicited by current injections. Exposure of slices for 15 min to 0.1 nM solution of these peptides resulted in an increase in the amplitude and slope of the EPSPs in 21 neurons (67%) tested. No consistent change in either the resting membrane potential or the input resistance of the neurons was observed. The peptide-induced increase in EPSPs reached a maximum 30-45 min after peptide application. In 14 of these neurons (66%), the peptide-induced increase in EPSPs remained throughout the entire 60-120 min washout period. In the remaining 7 neurons (33%), the initial increase in EPSPs amplitude was followed by a gradual decline to the pre-administration level. The increase in EPSP amplitude was often, but not always, associated with a decrease in the threshold and increase in the number of action potentials in response to depolarizing current injection. Suppression of GABAA receptor-mediated inhibition and N-methyl-D-aspartate (NMDA) receptor-mediated excitation did not prevent the effects of VP and VP(4-8) on the EPSP amplitude or the threshold for action potentials. The results demonstrate that 0.1 nM concentrations of these neuropeptides can elicit a long-lasting enhancement of the excitability of CA1/subiculum neurons of the ventral hippocampus to excitatory, glutamatergic synaptic input. This novel action of VP and its metabolite in the ventral hippocampus may be the physiological action, mediating the memory-enhancing effect of these peptides.
authors.affiliation: Rudolf Magnus Institute for Neurosciences, University of Utrecht, Netherlands.
authors.forename: A N
authors.initials: AN
authors.lastname: Chepkova
authors.forename: P
authors.initials: P
authors.lastname: French
authors.forename: D
authors.initials: D
authors.lastname: De Wied
authors.forename: A H
authors.initials: AH
authors.lastname: Ontskul
authors.forename: G M
authors.initials: GM
authors.lastname: Ramakers
authors.forename: V G
authors.initials: VG
authors.lastname: Skrebitski
authors.forename: W H
authors.initials: WH
authors.lastname: Gispen
authors.forename: I J
authors.initials: IJ
authors.lastname: Urban
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D014667:Vasopressins / Q000494:pharmacology*
chemical_list: D006727:Hormone Antagonists; D010446:Peptide Fragments; D017981:Receptors, Neurotransmitter; D014667:Vasopressins; D001127:Arginine Vasopressin; C072508:argipressin (4-8)