Altered hippocampal long-term synaptic plasticity in mice deficient in the PGE2 EP2 receptor.

Yang H, Zhang J, Breyer RM, Chen C
J Neurochem. 2009 108 (1): 295-304

PMID: 19012750 · PMCID: PMC2605769 · DOI:10.1111/j.1471-4159.2008.05766.x

Our laboratory demonstrated previously that PGE2-induced modulation of hippocampal synaptic transmission is via a pre-synaptic PGE2 EP2 receptor. However, little is known about whether the EP2 receptor is involved in hippocampal long-term synaptic plasticity and cognitive function. Here we show that long-term potentiation at the hippocampal perforant path synapses was impaired in mice deficient in the EP2 (KO), while membrane excitability and passive properties in granule neurons were normal. Importantly, escape latency in the water maze in EP2 KO was longer than that in age-matched EP2 wild-type littermates (WT). We also observed that long-term potentiation was potentiated in EP2 WT animals that received lipopolysaccharide (LPS, i.p.), but not in EP2 KO. Bath application of PGE2 or butaprost, an EP2 receptor agonist, increased synaptic transmission and decreased paired-pulses ratio in EP2 WT mice, but failed to induce the changes in EP2 KO mice. Meanwhile, synaptic transmission was elevated by application of forskolin, an adenylyl cyclase activator, both in EP2 KO and WT animals. In addition, the PGE2-enhanced synaptic transmission was significantly attenuated by application of PKA, IP3 or MAPK inhibitors in EP2 WT animals. Our results show that hippocampal long-term synaptic plasticity is impaired in mice deficient in the EP2, suggesting that PGE2-EP2 signaling is important for hippocampal long-term synaptic plasticity and cognitive function.

MeSH Terms (28)

Alprostadil Animals Animals, Newborn Colforsin Cyclooxygenase Inhibitors Dinoprostone Electric Stimulation Enzyme Inhibitors Excitatory Postsynaptic Potentials Hippocampus In Vitro Techniques Long-Term Potentiation Maze Learning Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Neurons Nitrobenzenes Patch-Clamp Techniques Physical Phenomena Reaction Time Receptors, Prostaglandin E Receptors, Prostaglandin E, EP2 Subtype Signal Transduction Sulfonamides Synapses Time Factors

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