Involvement of protein kinase A in patterning of the mouse somatosensory cortex.
Patterning of the mouse somatosensory cortex is unusually evident because of the presence of a "barrel field." Presynaptic serotonin and postsynaptic glutamate receptors regulate barrel formation, but little is known of the intracellular signaling pathways through which they act. To determine whether protein kinase A (PKA) plays a role in the development of the barrel field, we examined five viable PKA subunit-specific knock-out (KO) mouse lines for barrel field abnormalities. Barrels are present in these mice, but those lacking the RIIbeta subunit display significantly reduced contrast between the cell densities of barrel hollows and sides compared with wild-type animals. Thalamocortical afferent segregation in the posterior medial barrel subfield appeared normal, suggesting a postsynaptic site of gene action for the RIIbeta protein. Immunoelectron microscopy confirmed that RIIbeta was selectively localized to dendrites and dendritic spines. Mice lacking RIIbeta show reduced glutamate receptor A (GluRA) subunit insertion into the postsynaptic density in postnatal day 7 somatosensory cortex; however, GluRA KO mice developed normal barrels. Our results clearly demonstrate a role for postsynaptic PKA signaling pathways in barrel differentiation. They also demonstrate a clear dissociation between the regulation of GluRA trafficking by PKA and its role in barrel formation. Finally, although a role for PKA downstream of cAMP cannot be ruled out, these data suggest that PKA may not be the principle downstream target because none of the mutants showed a barrelless phenotype similar to that observed in adenylate cyclase type 1 KO mice. These results give insight into activity-dependent mechanisms that regulate barrel formation.
Watson
Ruth F
RF
Centre for Integrative Physiology, University of Edinburgh, Edinburgh EH8 9XD, United Kingdom.
Abdel-Majid
Raja M
RM
Barnett
Mark W
MW
Willis
Brandon S
BS
Katsnelson
Alla
A
Gillingwater
Thomas H
TH
McKnight
G Stanley
GS
Kind
Peter C
PC
Neumann
Paul E
PE
D000818:Animals; D000831:Animals, Newborn; D019521:Body Patterning / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics*; D049229:Dendritic Spines / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009421:Nervous System Malformations / Q000201:enzymology* / Q000235:genetics*; D009434:Neural Pathways / Q000002:abnormalities / Q000201:enzymology; D021122:Protein Subunits / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013003:Somatosensory Cortex / Q000002:abnormalities* / Q000201:enzymology*; D013570:Synaptic Membranes / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics; D020651:Ventral Thalamic Nuclei / Q000002:abnormalities / Q000201:enzymology
D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases