Barrel map development relies on protein kinase A regulatory subunit II beta-mediated cAMP signaling

J Neurosci. 2006 Apr 19;26(16):4338-49. doi: 10.1523/JNEUROSCI.3745-05.2006.

Abstract

The cellular and molecular mechanisms mediating the activity-dependent development of brain circuitry are still incompletely understood. Here, we examine the role of cAMP-dependent protein kinase [protein kinase A (PKA)] signaling in cortical development and plasticity, focusing on its role in thalamocortical synapse and barrel map development. We provide direct evidence that PKA activity mediates barrel map formation using knock-out mice that lack type IIbeta regulatory subunits of PKA (PKARIIbeta). We show that PKARIIbeta-mediated PKA function is required for proper dendritogenesis and the organization of cortical layer IV neurons into barrels, but not for the development and plasticity of thalamocortical afferent clustering into a barrel pattern. We localize PKARIIbeta function to postsynaptic processes in barrel cortex and show that postsynaptic PKA targets, but not presynaptic PKA targets, have decreased phosphorylation in pkar2b knock-out (PKARIIbeta(-/-)) mice. We also show that long-term potentiation at TC synapses and the associated developmental increase in AMPA receptor function at these synapses, which normally occurs as barrels form, is absent in PKARIIbeta(-/-) mice. Together, these experiments support an activity-dependent model for barrel map development in which the selective addition and elimination of thalamocortical synapses based on Hebbian mechanisms for synapse formation is mediated by a cAMP/PKA-dependent pathway that relies on PKARIIbeta function.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / enzymology
  • Cerebral Cortex / growth & development*
  • Cyclic AMP / pharmacology
  • Cyclic AMP / physiology*
  • Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit
  • Cyclic AMP-Dependent Protein Kinases / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Protein Subunits / physiology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Thalamus / drug effects
  • Thalamus / enzymology
  • Thalamus / growth & development*

Substances

  • Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit
  • Prkar2b protein, mouse
  • Protein Subunits
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases