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  Phosphodiesterase 1 bridges glutamate inputs with NO- and dopamine-induced cyclic nucleotide signals in the striatum

Betolngar, D. B., Mota, E., Fabritius, A., Nielsen, J., Hougaard, C., Christoffersen, C. T., et al. (2019). Phosphodiesterase 1 bridges glutamate inputs with NO- and dopamine-induced cyclic nucleotide signals in the striatum. Cerebral Cortex, 29(12), 5022-5036. doi:10.1093/cercor/bhz041.

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 Creators:
Betolngar, Dahdjim B., Author
Mota, Elia, Author
Fabritius, Arne1, Author           
Nielsen, Jacob, Author
Hougaard, Charlotte, Author
Christoffersen, Claus T., Author
Yang, Jun, Author
Kehler, Jan, Author
Griesbeck, Oliver1, Author           
Castro V, Liliana R., Author
Vincent, Pierre, Author
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1Research Group: Tools for Bio-Imaging / Griesbeck, MPI of Neurobiology, Max Planck Society, ou_1113560              

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Free keywords: LEVODOPA-INDUCED DYSKINESIAS; NITRIC OXIDE/CGMP PATHWAY; IN-VIVO; HEMIPARKINSONIAN RATS; PHASIC DOPAMINE; DOWN-REGULATION; CGMP; BRAIN; INHIBITORS; MODULATIONbiosensor imaging; calcium; cAMP; cGMP; synaptic plasticity;
 Abstract: The calcium-regulated phosphodiesterase 1 (PDE1) family is highly expressed in the brain, but its functional role in neurones is poorly understood. Using the selective PDE1 inhibitor Lu AF64196 and biosensors for cyclic nucleotides including a novel biosensor for cGMP, we analyzed the effect of PDE1 on cAMP and cGMP in individual neurones in brain slices from male newborn mice. Release of caged NMDA triggered a transient increase of intracellular calcium, which was associated with a decrease in cAMP and cGMP in medium spiny neurones in the striatum. Lu AF64196 alone did not increase neuronal cyclic nucleotide levels, but blocked the NMDA-induced reduction in cyclic nucleotides indicating that this was mediated by calcium-activated PDE1. Similar effects were observed in the prefrontal cortex and the hippocampus. Upon corelease of dopamine and NMDA, PDE1 was shown to down-regulate the D-1-receptor mediated increase in cAMP. PDE1 inhibition increased long-term potentiation in rat ventral striatum, showing that PDE1 is implicated in the regulation of synaptic plasticity. Overall, our results show that PDE1 reduces cyclic nucleotide signaling in the context of glutamate and dopamine coincidence. This effect could have a therapeutic value for treating brain disorders related to dysfunctions in dopamine neuromodulation.

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Language(s): eng - English
 Dates: 2019-12-01
 Publication Status: Published in print
 Pages: 15
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000506813900009
DOI: 10.1093/cercor/bhz041
 Degree: -

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Title: Cerebral Cortex
Source Genre: Journal
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Publ. Info: New York, NY : Oxford University Press
Pages: - Volume / Issue: 29 (12) Sequence Number: - Start / End Page: 5022 - 5036 Identifier: ISSN: 1047-3211
CoNE: https://pure.mpg.de/cone/journals/resource/954925592440