| First Author | Inan M | Year | 2006 |
| Journal | J Neurosci | Volume | 26 |
| Issue | 16 | Pages | 4338-49 |
| PubMed ID | 16624954 | Mgi Jnum | J:108357 |
| Mgi Id | MGI:3623823 | Doi | 10.1523/JNEUROSCI.3745-05.2006 |
| Citation | Inan M, et al. (2006) Barrel map development relies on protein kinase A regulatory subunit II beta-mediated cAMP signaling. J Neurosci 26(16):4338-49 |
| abstractText | 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. |
