Type VI adenylyl cyclase negatively regulates GluN2B-mediated LTD and spatial reversal learning View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-03-02

AUTHORS

Ching-Pang Chang, Cheng-Ta Lee, Wen-Hsien Hou, Meng-Syuan Lin, Hsing-Lin Lai, Chen-Li Chien, Chen Chang, Pei-Lin Cheng, Cheng-Chang Lien, Yijuang Chern

ABSTRACT

The calcium-sensitive type VI adenylyl cyclase (AC6) is a membrane-bound adenylyl cyclase (AC) that converts ATP to cAMP under stimulation. It is a calcium-inhibited AC and integrates negative inputs from Ca(2+) and multiple other signals to regulate the intracellular cAMP level. In the present study, we demonstrate that AC6 functions upstream of CREB and negatively controls neuronal plasticity in the hippocampus. Genetic removal of AC6 leads to cyclase-independent and N-terminus of AC6 (AC6N)-dependent elevation of CREB expression, and enhances the expression of GluN2B-containing NMDA receptors in hippocampal neurons. Consequently, GluN2B-dependent calcium signaling and excitatory postsynaptic current, long-term depression, and spatial reversal learning are enhanced in the hippocampus of AC6(-/-) mice without altering the gross anatomy of the brain. Together, our results suggest that AC6 negatively regulates neuronal plasticity by modulating the levels of CREB and GluN2B in the hippocampus. More... »

PAGES

22529

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep22529

DOI

http://dx.doi.org/10.1038/srep22529

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022775450

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26932446


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