VIP, a modulator of synaptic transmission present in hippocampal interneurones, was shown to inhibit long-term potentiation in the CA1 area of the rat hippocampus through activation of VPAC1 receptors (1). VIP release is triggered by electrical activity, VIP receptors are enhanced in TLE patients (2) and VIP promotes neuronal survival in the absence of electrical activity (3), a situation observed during hypoxic depression. In this work we investigated if VPAC1 receptor activation during brief hypoxia and in vitro interictal-like activity could influence the subsequent expression of LTP 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. Hypoxia was induced by 3 min superfusion with 95% N2-5% CO2 (normoxia: 95% O2-5% CO2). In vitro interictal-like activity was induced by 30 min superfusion with aCSF containing no 0mM MgCl2 and 6mM KCl (normal comp.: 1mM MgCl2 and 3mM KCl). LTP was induced by θ-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 both insults. Student’s t test was used to evaluate the statistical differences between control and test groups. Θ-burst stimulation in control conditions induced a long-lasting enhancement of fEPSP slope (29.0±2.9%, n=7, 50-60 min after stimulation). Hypoxia caused a brief but marked decrease in fEPSP slope that recovered to basal values 30 min after hypoxia in control conditions but was not complete (89.0±1.8%) after hypoxia in the presence of 100nM PG 97-269. Θ-burst-induced LTP was enhanced to 44.9±1.3% (n=4) and 43.8±1.3% (n=4) when θ-burst stimulation was delivered 30 min and 60 min after hypoxia, respectively. This enhancement was not observed in slices subjected to hypoxia in the presence of PG 97-269 (100nM). Following interictal-like activity induced by 0Mg2+ aCSF, θ-burst-induced LTP was impaired to 17.9±2.3% (n=3) and 24.8±1.5% (n=3) when evoked 30 min 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). These results suggest that activation of VPAC1 receptors by endogenous VIP during brief hypoxia contributes to a subsequent facilitation of LTP induction. In contrast, activation of VPAC1 receptors during interictal-like seizures may contribute to the inhibition of LTP that follows this insult.