Phosphodiesterase 1b (PDE1B) Regulates Spatial and Contextual Memory in Hippocampus

Overview

Journal Front Mol Neurosci

Specialty Molecular Biology

Date 2019 Feb 23

PMID 30792627

Citations 10

Authors

Susan McQuown

Shouzhen Xia

Karsten Baumgartel

Richard Barido

Gary Anderson

Brian Dyck

Roderick Scott

Marco Peters

Affiliations

Soon will be listed here.

Abstract

Augmentation of cyclic nucleotide signaling through inhibition of phosphodiesterase (PDE) activity has long been understood to enhance memory. Efforts in this domain have focused predominantly on PDE4, a cAMP-specific phosphodiesterase implicated in consolidation. But less is known about the function of other PDEs expressed in neuroanatomical regions critical to memory. The PDE1 isoforms are the only PDEs to regulate neuronal cAMP and cGMP levels in a Ca/Calmodulin (CaM) dependent manner. Here, we show that knock-down of PDE1B in hippocampus of adult mice enhances contextual and spatial memory without effect on non-cognitive behaviors. Pharmacological augmentation of memory in rats was observed with a selective inhibitor of PDE1 dosed before and immediately after training, but not with drug dosed either 1 h after training or before recall. Our data clearly demonstrate a role for the PDE1B isoforms as negative regulators of memory, and they implicate PDE1 in an early phase of consolidation, but not retrieval. Inhibition of PDE1B is a promising therapeutic mechanism for treating memory impairment.

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