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.
Lu
Hui-Chen
HC
Department of Neuroscience, Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA. hclu@bcm.tmc.edu
Butts
Daniel A
DA
Kaeser
Pascal S
PS
She
Wei-Chi
WC
Janz
Roger
R
Crair
Michael C
MC
D000262:Adenylyl Cyclases / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D001931:Brain Mapping; D002118:Calcium / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008959:Models, Neurological; D016202:N-Methylaspartate / Q000494:pharmacology; D009434:Neural Pathways / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000235:genetics; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D013003:Somatosensory Cortex / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D016704:Synapsins / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism*; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018377:Neurotransmitter Agents; C491490:Rims1 protein, mouse; D016704:Synapsins; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1; D002118:Calcium