{1494} revision 2 modified: 01-07-2020 03:43 gmt

PMID-25258080 A critical time window for dopamine actions on the structural plasticity of dendritic spines

  • Remarkably short time window for dopamine to modulate / modify (aggressive) STDP protocol.
  • Showed with the low-affinity calcium indicator Fluo4-FF that peak calcium concentrations in spines is not affected by optogenetic stimulation of dopamine fibers.
  • However, CaMKII activity is modulated by DA activity -- when glutamate uncaging and depolarization was followed by optogenetic stimulation of DA fibers followed, the FRET sensor Camui-CR reported significant increases of CaMKII activity.
  • This increase was abolished by the application of DRAPP-32 inhibiting peptide, which blocks the interaction of dopamine and cAMP-regulated phospoprotein - 32kDa (DRAPP-32) with protein phosphatase 1 (PP-1)
    • Spine enlargement was induced in the absence of optogenetic dopamine when PP-1 was inhibited by calculin A...
    • Hence, phosphorylation of DRAPP-32 by PKA inhibits PP-1 and disinihibts CaMKII. (This causal inference seems loopy; they reference a hippocampal paper, [18])
  • To further test this, they used a FRET probe of PKA activity, AKAR2-CR. This sensor showed that PKA activity extends throughout the dendrite, not just the stimulated spine, and can respond to DA release directly.