Requirement for the RIIbeta isoform of PKA, but not calcium-stimulated adenylyl cyclase, in visual cortical plasticity.
The cAMP-dependent protein kinase (PKA) signaling pathway plays a key role in visual cortical plasticity. Inhibitors that block activation of all PKA regulatory subunits (RIalpha,RIbeta, RIIalpha, RIIbeta) abolish long-term potentiation (LTP) and long-term depression (LTD) in vitro and ocular dominance plasticity (ODP) in vivo. The details of this signaling cascade, however, including the source of PKA signals and which PKA subunits are involved, are unknown. To investigate these issues we have examined LTP, LTD, and ODP in knock-out mice lacking either the two cortically expressed Ca2+-stimulated adenylyl cyclases (AC1 and AC8) or the predominant neocortical subunit of PKA (RIIbeta). Here we show that plasticity remains intact in AC1/AC8-/- mice, whereas ODP and LTD, but not LTP, are absent in RIIbeta-/- mice. We conclude that (1) plasticity in the visual cortex does not require the activity of known Ca2+-stimulated adenylyl cyclases, (2) the PKA dependence of ODP and LTD, but not LTP, is mediated by RIIbeta-PKA, and (3) multiple isoforms of PKA contribute to LTD.
Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut 06520-8061, USA. quentin.fischer@yale.edu
Quentin S
QS
Fischer
Christopher J
CJ
Beaver
Yupeng
Y
Yang
Yan
Y
Rao
Klara B
KB
Jakobsdottir
Daniel R
DR
Storm
G Stanley
GS
McKnight
Nigel W
NW
Daw
D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D023882:Dominance, Ocular / Q000235:genetics / Q000502:physiology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000235:genetics / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D012683:Sensory Deprivation / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology; D014793:Visual Cortex / Q000378:metabolism / Q000502:physiology*
D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; D007527:Isoenzymes; C517838:Prkar2b protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1; C118292:adenylyl cyclase 8; D002118:Calcium