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Neuropharmacology. 2013 Nov;74:86-95. doi: 10.1016/j.neuropharm.2013.01.011. Epub 2013 Jan 25.

The role of phosphodiesterases in hippocampal synaptic plasticity.

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Dept. of Brain & Cognitive Sciences, College of Natural Sciences, Seoul National University, Gwanak-gu, Seoul 151-746, South Korea.


Phosphodiesterases (PDEs) degrade cyclic nucleotides, signalling molecules that play important roles in synaptic plasticity and memory. Inhibition of PDEs may therefore enhance synaptic plasticity and memory as a result of elevated levels of these signalling molecules, and this has led to interest in PDE inhibitors as cognitive enhancers. The development of new mouse models in which PDE subtypes have been selectively knocked out and increasing selectivity of PDE antagonists means that this field is currently expanding. Roles for PDE2, 4, 5 and 9 in synaptic plasticity have so far been demonstrated and we review these studies here in the context of cyclic nucleotide signalling more generally. The role of other PDE families in synaptic plasticity has not yet been investigated, and this area promises to advance our understanding of cyclic nucleotide signalling in synaptic plasticity in the future. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'.


Cyclic nucleotides; Depotentiation; Hippocampus; LTD; LTP; Phosphodiesterases; Synaptic plasticity; cAMP; cGMP

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