Essential role for synaptopodin in dendritic spine plasticity of the developing hippocampus

J Neurosci. 2013 Jul 24;33(30):12510-8. doi: 10.1523/JNEUROSCI.2983-12.2013.

Abstract

Dendritic spines are a major substrate of brain plasticity. Although many studies have focused on Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-mediated regulation of spine dynamics and synaptic function in adult brain, much less is know about protein kinase A (PKA)-dependent regulation of spine shape dynamics during postnatal brain development. Synaptopodin is a dendritic spine associated modulator of actin dynamics and a substrate of PKA. Here we show that NMDA and cAMP-induced dendritic spine expansion is impaired in hippocampal slices from 15- and 21-d-old synaptopodin-deficient mice. We further show that synaptopodin is required for full expression of PKA-dependent hippocampal long-term potentiation in 15- and 21-d-old, but not adult, mice. PKA-induced cAMP response element-binding phosphorylation is normal in the hippocampus of synaptopodin-deficient mice, suggesting that synaptopodin functions independently of cAMP response element-binding. Our results identify synaptopodin as a substrate of PKA in hippocampal neurons and point to an essential role for synaptopodin in activity-dependent regulation of dendritic spine dynamics and synaptic plasticity in postnatal brain development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cyclic AMP / metabolism
  • Cyclic AMP / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dendritic Spines / physiology*
  • Electrophysiology
  • Excitatory Amino Acid Agonists / pharmacology
  • Female
  • Hippocampus / growth & development*
  • Hippocampus / physiology*
  • Isoquinolines / pharmacology
  • Long-Term Potentiation / physiology
  • Male
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microfilament Proteins / genetics
  • Microfilament Proteins / physiology*
  • N-Methylaspartate / pharmacology
  • Neuronal Plasticity / physiology*
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / physiology
  • Protein Kinase Inhibitors / pharmacology
  • Substrate Specificity
  • Sulfonamides / pharmacology

Substances

  • Excitatory Amino Acid Agonists
  • Isoquinolines
  • Microfilament Proteins
  • Protein Kinase Inhibitors
  • Sulfonamides
  • Synpo protein, mouse
  • N-Methylaspartate
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide