Adenylyl cyclase I regulates AMPA receptor trafficking during mouse cortical 'barrel' map development.
Cortical map formation requires the accurate targeting, synaptogenesis, elaboration and refinement of thalamocortical afferents. Here we demonstrate the role of Ca2+/calmodulin-activated type-I adenylyl cyclase (AC1) in regulating the strength of thalamocortical synapses through modulation of AMPA receptor (AMPAR) trafficking using barrelless mice, a mutant without AC1 activity or cortical 'barrel' maps. Barrelless synapses are stuck in an immature state that contains few functional AMPARs that are rarely silent (NMDAR-only). Long-term potentiation (LTP) and long-term depression (LTD) at thalamocortical synapses require postsynaptic protein kinase A (PKA) activity and are difficult to induce in barrelless mice, probably due to an inability to properly regulate synaptic AMPAR trafficking. Consistent with this, both the extent of PKA phosphorylation on AMPAR subunit GluR1 and the expression of surface GluR1 are reduced in barrelless neurons. These results suggest that activity-dependent mechanisms operate through an AC1/PKA signaling pathway to target some synapses for consolidation and others for elimination during barrel map formation.
Lu
Hui-Chen
HC
Division of Neuroscience and Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza S-603, Houston, Texas 77030, USA. hlu@cns.tmc.edu
She
Wei-Chi
WC
Plas
Daniel T
DT
Neumann
Paul E
PE
Janz
Roger
R
Crair
Michael C
MC
D000262:Adenylyl Cyclases / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001931:Brain Mapping; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000254:growth & development* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D017774:Long-Term Potentiation / Q000235:genetics; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains; D021381:Protein Transport / Q000235:genetics; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
D018091:Receptors, AMPA; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1