Adenylyl cyclase I regulates AMPA receptor trafficking during mouse cortical 'barrel' map development
Copyright policy )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.
- Baylor College of Medicine United States
- Dalhousie University Canada
- The University of Texas System United States
- The University of Texas Health Science Center at Houston United States
Cerebral Cortex, Brain Mapping, Mice, Inbred ICR, Long-Term Potentiation, Gene Expression Regulation, Developmental, Mice, Mutant Strains, Membrane Potentials, Mice, Inbred C57BL, Mice, Protein Transport, Animals, Newborn, Animals, Receptors, AMPA, Cells, Cultured, Adenylyl Cyclases, Signal Transduction
Cerebral Cortex, Brain Mapping, Mice, Inbred ICR, Long-Term Potentiation, Gene Expression Regulation, Developmental, Mice, Mutant Strains, Membrane Potentials, Mice, Inbred C57BL, Mice, Protein Transport, Animals, Newborn, Animals, Receptors, AMPA, Cells, Cultured, Adenylyl Cyclases, Signal Transduction
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