RT Journal Article
SR Electronic
T1 Requirement for the RIIβ Isoform of PKA, But Not Calcium-Stimulated Adenylyl Cyclase, in Visual Cortical Plasticity
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9049
OP 9058
DO 10.1523/JNEUROSCI.2409-04.2004
VO 24
IS 41
A1 Quentin S. Fischer
A1 Christopher J. Beaver
A1 Yupeng Yang
A1 Yan Rao
A1 Klara B. Jakobsdottir
A1 Daniel R. Storm
A1 G. Stanley McKnight
A1 Nigel W. Daw
YR 2004
UL http://www.jneurosci.org/content/24/41/9049.abstract
AB 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 (RIα,RIβ, RIIα, RIIβ) 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 (RIIβ). Here we show that plasticity remains intact in AC1/AC8-/- mice, whereas ODP and LTD, but not LTP, are absent in RIIβ-/- 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 RIIβ-PKA, and (3) multiple isoforms of PKA contribute to LTD.