Nature Neuroscience6, 939 - 947 (2003)
Published online: 3 August 2003; | doi:10.1038/nn1106
Adenylyl cyclase I regulates AMPA receptor trafficking during mouse cortical 'barrel' map development
Hui-Chen Lu1, Wei-Chi She1, Daniel T Plas1, Paul E Neumann2, Roger Janz3
& Michael C Crair1
1
Division of Neuroscience and Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza S-603, Houston, Texas 77030, USA.
2
Department of Anatomy & Neurobiology, Faculty of Medicine, Dalhousie University, 5850 College Street, Halifax, Nova Scotia B3H 1X5, Canada.
3
Department of Neurobiology and Anatomy, W.M. Keck Center for the Neurobiology of Learning and Memory, University of Texas-Houston Medical School, 6431 Fannin Street, Houston, Texas 77030, USA.
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.
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