Cortical adenylyl cyclase 1 is required for thalamocortical synapse maturation and aspects of layer IV barrel development.
Experimental evidence from mutant or genetically altered mice indicates that the formation of barrels and the proper maturation of thalamocortical (TC) synapses in the primary somatosensory (barrel) cortex depend on mechanisms mediated by neural activity. Type 1 adenylyl cyclase (AC1), which catalyzes the formation of cAMP, is stimulated by increases in intracellular Ca(2+) levels in an activity-dependent manner. The AC1 mutant mouse, barrelless (brl), lacks typical barrel cytoarchitecture, and displays presynaptic and postsynaptic functional defects at TC synapses. However, because AC1 is expressed throughout the trigeminal pathway, the barrel cortex phenotype of brl mice may be a consequence of AC1 disruption in cortical or subcortical regions. To examine the role of cortical AC1 in the development of morphological barrels and TC synapses, we generated cortex-specific AC1 knock-out (CxAC1KO) mice. We found that neurons in layer IV form grossly normal barrels and TC axons fill barrel hollows in CxAC1KO mice. In addition, whisker lesion-induced critical period plasticity was not impaired in these mice. However, we found quantitative reductions in the quality of cortical barrel cytoarchitecture and dendritic asymmetry of layer IV barrel neurons in CxAC1KO mice. Electrophysiologically, CxAC1KO mice have deficits in the postsynaptic but not in the presynaptic maturation of TC synapses. These results suggest that activity-dependent postsynaptic AC1-cAMP signaling is required for functional maturation of TC synapses and the development of normal barrel cortex cytoarchitecture. They also suggest that the formation of the gross morphological features of barrels is independent of postsynaptic AC1 in the barrel cortex.
Iwasato
Takuji
T
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Saitama 351-0198, Japan.
Inan
Melis
M
Kanki
Hiroaki
H
Erzurumlu
Reha S
RS
Itohara
Shigeyoshi
S
Crair
Michael C
MC
D000262:Adenylyl Cyclases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology* / Q000254:growth & development* / Q000648:ultrastructure; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009434:Neural Pathways / Q000201:enzymology / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology; D013569:Synapses / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D013788:Thalamus / Q000201:enzymology* / Q000254:growth & development* / Q000648:ultrastructure
D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1