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,Cyt~']VP(4-9) and [pGlu4,Cyt~']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 CA 1/subiculum of lhe ventral hippocampus. The EPSPs were evoked by stimulating the stratum radiatum of the CAI 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%1, the initial increase in EPSPs amplitude was followed by a gradual decline to the pre-adminislralion 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 lo depolarizing current injection. Suppression of GABA a 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 CAl/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.

Estrogen receptors mediate estradiol's effect on sensitization and CPP to cocaine in female rats: Role of contextual cues

“…Cognitive enhancers facilitate processes of learning and memory, and may do so by boosting attention and memory consolidation (Tuboly and Vécsei, 2013). Drugs, such as amphetamine and methylphenidate, exercise, sleep, certain foods and hormones enhance cognitive performance (Chen et al, 2011), (Chepkova et al, 1995; Ramanathan et al, 2012) (for review see Tuboly and Vécsei, 2013). Estradiol shares several intracellular pathways with cognitive processes, such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase /protein kinase B (P13K/Akt) (D’Astous et al, 2006; Chan and Ye, 2012).…”

Learning About Oxytocin: Pharmacologic and Behavioral Issues

“…It can therefore be postulated that OT fibers are present at puberty and then disappear or that it is AVP that physiologically mediates these effects. It is known that AVP plays a role in the hippocampal activity-dependent plasticity mediated by V1aRs and V1bRs (89,(96)(97)(98)(99), and the use of high concentrations of agonists and antagonists in the above-mentioned studies does not rule out the possibility of overlapping V1aR/V1bR-mediated effects. Further studies are required to assess if OT has a direct effect on the activity-dependent synaptic plasticity involved in LTP and/or long-term depression (the neurobiological substrates of memory), or if it participates in learning and memory processes by acting on other neurotransmitters/neuromodulators.…”

Vasopressin facilitates GABAergic transmission in rat hippocampus via activation of V1A receptors

“…In line with our results, previous work has also shown that AVP excites hippocampal pyramidal neurons (Mizuno et al, 1984; Muhlethaler et al, 1982; Tiberiis et al, 1983a). Furthermore, AVP has been shown to increase LTP in CA1 region (Chepkova et al, 1995; Chepkova et al, 2001; Rong et al, 1993) and the dentate gyrus (Chen et al, 1993; Dubrovsky et al, 2003). AVP-mediated direct excitation of CA1 pyramidal neurons and indirect augmentation of glutamatergic transmission onto CA1 pyramidal neurons likely contribute to AVP-induced enhancement of learning and memory (Alescio-Lautier et al, 2000; Alescio-Lautier and Soumireu-Mourat, 1998).…”

“…In addition, the hippocampus also expresses high-density of vasopressin receptors (Audigier and Barberis, 1985; Brinton et al, 1984; Costantini and Pearlmutter, 1984; De Kloet et al, 1985). Consistent with the distribution of vasopressin and vasopressin receptors in the hippocampus, application of vasopressin enhances synaptic transmission and induces long-term potentiation (LTP) in CA1 region (Chepkova et al, 1995; Chepkova et al, 2001; Rong et al, 1993) and the dentate gyrus (Chen et al, 1993; Dubrovsky et al, 2003). Whereas vasopressin has been shown to excite hippocampal pyramidal neurons (Mizuno et al, 1984; Muhlethaler et al, 1982; Tiberiis et al, 1983a), recordings of the field potentials demonstrate that the pyramidal discharge is inhibited by vasopressin (Albeck and Smock, 1988) suggesting that vasopressin also excites non-pyramidal inhibitory interneurons to exert indirect inhibitory effects on pyramidal neurons (Muhlethaler et al, 1984).…”