Endogenous VIP VPAC1 receptor activation during ictal and interictal-like activity induced in vitro by biccuculine and 0-Mg2+ modulates subsequent LTP expression in the rat hippocampus.
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1
Institute of Biosystems and Integrative Sciences (BioISI), Portugal
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2
Center for Chemistry and Biochemistry, Faculty of Sciences, University of Lisbon, Portugal
VIP inhibits long-term potentiation in the CA1 area of the rat hippocampus through activation of VPAC1 receptors(1). VIP release is triggered by electrical activity and VIP receptors are enhanced in TLE patients(2). In this work we investigated if VPAC1 receptor activation during in vitro interictal-like activity (ILA), such as the observed during epileptogenesis, could influence the subsequent expression of LTP and GABAergic, glutamatergic and lipid raft synaptic markers in the CA1 area of the hippocampus.
Male wistar rats (6-7 week-old) were decapitated under fluothane anaesthesia. Extracellular electrophysiological recordings of field-excitatory post-synaptic potentials (fEPSPs) evoked by electrical stimulation in hippocampal slices were used to access synaptic transmission. In vitro ILA was induced by 30 min superfusion with aCSF containing 0mM MgCl2 and 6mM KCl (in normal comp.: 1mM MgCl2 and 3mM KCl). LTP was induced by theta-burst stimulation (five 100Hz bursts, 4 stimuli, separated by 200 ms) and potentiation of fEPSP slope evaluated 50-60 min after LTP induction. The selective VPAC1 antagonist PG 97-269 was used to block endogenous VPAC1 receptor activation during ILA. Glutamatergic, GABAergic and lipid raft synaptic markers were evaluated by western-blot in hippocampal synaptosomes obtained from these slices. ANOVA was used to evaluate the statistical differences among different experimental conditions.
Theta-burst stimulation in control conditions induced a long-lasting enhancement of fEPSP slope (29.0±2.9%, n=7, 50-60 min after stimulation). Following ILA induced by 0Mg2+ aCSF, this enhancement was impaired to 17.9±2.3% (n=3) and 24.8±1.5% (n=3) when LTP was induced 30 and 60 min after interictal-like activity, respectively. When interictal-like activity was induced in the presence of PG 97-269 (100nM), this impairment was not observed (n=3). The expression of gephyrin, PSD-95 and flotilin was enhanced 50min after 0Mg2+ exposure while expression of caveolin was decreased. The presence of PG 97-269 (100nM) during 0Mg2+ exposure enhanced this effect for gephyrin and flotilin while it attenuated the enhancement in PSD-95 and caused no change on caveolin expression.
These results suggest that activation of VPAC1 receptors by endogenous VIP during interictal-like activity may contribute to the inhibition of LTP that follows and this could be an usefull therapeutic target in epileptogenesis.
Acknowledgements
Supported by FCT (SFRH/ BPD/81358/2011; PTDC/SAU-PUB/28311/2017).
References
1 – Cunha-Reis, D et al., J Mol Neurosci, 2010. 42: 278. 2 – de Lanerolle NC et al., Br Res, 1995. 686: 182-93.
Keywords:
VIP (vasoactive intestinal peptide),
Epilepsy,
LTP (Long Term Potentiation),
Interictal activity,
lipid rafts
Conference:
XVI Meeting of the Portuguese Society for Neuroscience (SPN2019), Lisboa, Portugal, 30 May - 1 Jun, 2019.
Presentation Type:
Poster presentation
Topic:
Cellular and Molecular Neurosciences
Citation:
Carvalho-Rosa
J and
Cunha-Reis
D
(2019). Endogenous VIP VPAC1 receptor activation during ictal and interictal-like activity induced in vitro by biccuculine and 0-Mg2+ modulates subsequent LTP expression in the rat hippocampus..
Front. Cell. Neurosci.
Conference Abstract:
XVI Meeting of the Portuguese Society for Neuroscience (SPN2019).
doi: 10.3389/conf.fncel.2019.01.00028
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Received:
27 Feb 2019;
Published Online:
27 Sep 2019.
*
Correspondence:
Dr. José Diogo Carvalho-Rosa, Institute of Biosystems and Integrative Sciences (BioISI), Lisbon, Portugal, josediogocarvalhorosa@gmail.com