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PMID: 17151284 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Imaging of cAMP levels and protein kinase A activity reveals that retinal waves drive oscillations in second-messenger cascades.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 26 ·No. 49 ·2006-12-06 ·Pages 12807-15

Dunn TA, Wang CT, Colicos MA, Zaccolo M, DiPilato LM, Zhang J, Tsien RY, Feller MB

Abstract

Recent evidence demonstrates that low-frequency oscillations of intracellular calcium on timescales of seconds to minutes drive distinct aspects of neuronal development, but the mechanisms by which these calcium transients are coupled to signaling cascades are not well understood. Here we test the hypothesis that spontaneous electrical activity activates protein kinase A (PKA). We use live-cell indicators to observe spontaneous and evoked changes in cAMP levels and PKA activity in developing retinal neurons. Expression of cAMP and PKA indicators in neonatal rat retinal explants reveals spontaneous oscillations in PKA activity that are temporally correlated with spontaneous depolarizations associated with retinal waves. In response to short applications of forskolin, dopamine, or high-potassium concentration, we image an increase in cAMP levels and PKA activity, indicating that this second-messenger pathway can be activated quickly by neural activity. Depolarization-evoked increases in PKA activity were blocked by the removal of extracellular calcium, indicating that they are mediated by a calcium-dependent mechanism. These findings demonstrate for the first time that spontaneous activity in developing circuits is correlated with activation of the cAMP/PKA pathway and that PKA activity is turned on and off on the timescale of tens of seconds. These results show a link between neural activity and an intracellular biochemical cascade associated with plasticity, axon guidance, and neural differentiation.

MeSH Terms
Animals Animals, Newborn Cells, Cultured Cyclic AMP/analysis,metabolism Cyclic AMP-Dependent Protein Kinases/analysis,metabolism Enzyme Activation/physiology Fluorescence Resonance Energy Transfer Neurons/chemistry,metabolism Rats Retina/chemistry,physiology Second Messenger Systems/physiology
Chemicals
Cyclic AMP Cyclic AMP-Dependent Protein Kinases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Dunn Timothy A
Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093, USA.
Wang Chih-Tien
Colicos Michael A
Zaccolo Manuela
DiPilato Lisa M
Zhang Jin
Tsien Roger Y
Feller Marla B
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.3238-06.2006
Published
2006-12-06
Pages
12807-15
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC2931275
Subset
IM
Grants
NIDDK NIH HHS · F31 DK074381 · United States
NIDDK NIH HHS · R01 DK073368 · United States
NEI NIH HHS · R01 EY013528 · United States
NEI NIH HHS · EY016417 · United States
NEI NIH HHS · EY13528 · United States
NINDS NIH HHS · NS27177 · United States
NINDS NIH HHS · R01 NS027177 · United States
NEI NIH HHS · R01 EY013528-09 · United States
NINDS NIH HHS · R37 NS027177 · United States
NEI NIH HHS · R21 EY016417 · United States
NIDDK NIH HHS · DK73368 · United States
Telethon · TCP00089 · Italy
External Links
PubMed source DOI: 10.1523/JNEUROSCI.3238-06.2006 PMC Full Text View journal details
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