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Role of efficient neurotransmitter release in barrel map development.

Cortical maps are remarkably precise, with organized arrays of thalamocortical afferents (TCAs) that project into distinct neuronal modules. Here, we present evidence for the involvement of efficient neurotransmitter release in mouse cortical barrel map development using barrelless mice, a loss-of-function mutant of calcium/calmodulin-activated adenylyl cyclase I (AC1), and mice with a mutation in Rab3-interacting molecule 1alpha (RIM1alpha), an active zone protein that regulates neurotransmitter release. We demonstrate that release efficacy is substantially decreased in barrelless TCAs. We identify RIMs as important phosphorylation targets for AC1 in the presynaptic terminal. We further show that RIM1alpha mutant mice have reduced TCA neurotransmitter release efficacy and barrel map deficits, although not as severe as those found in barrelless mice. This supports the role of RIM proteins in mediating, in part, AC1 signaling in barrel map development. Finally, we present a model to show how inadequacies in presynaptic function can interfere with activity-dependent processes in neuronal circuit formation. These results demonstrate how efficient synaptic transmission mediated by AC1 function contributes to the development of cortical barrel maps.

Pubmed ID: 16525048 RIS Download

Mesh terms: Adenylyl Cyclases | Animals | Animals, Newborn | Blotting, Western | Brain Mapping | Calcium | Dizocilpine Maleate | Dose-Response Relationship, Drug | Drug Interactions | Electric Stimulation | Excitatory Amino Acid Agonists | Excitatory Amino Acid Antagonists | Excitatory Postsynaptic Potentials | GTP-Binding Proteins | Gene Expression Regulation, Developmental | In Vitro Techniques | Mice | Mice, Inbred C57BL | Mice, Knockout | Mice, Mutant Strains | Models, Neurological | N-Methylaspartate | Neural Pathways | Neuronal Plasticity | Neurotransmitter Agents | Patch-Clamp Techniques | Somatosensory Cortex | Synapsins | Thalamus | Time Factors | alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

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Associated grants

  • Agency: NINDS NIH HHS, Id: NS48884
  • Agency: NINDS NIH HHS, Id: R01 NS048884
  • Agency: NIMH NIH HHS, Id: MH62639
  • Agency: NEI NIH HHS, Id: R01 EY015788
  • Agency: NINDS NIH HHS, Id: F32 NS011034
  • Agency: NICHD NIH HHS, Id: HD24064

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