Abstract
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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenylyl Cyclases / genetics
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Animals
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Animals, Newborn
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Blotting, Western / methods
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Brain Mapping*
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Calcium / pharmacology
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Dizocilpine Maleate / pharmacology
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Dose-Response Relationship, Drug
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Drug Interactions
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Electric Stimulation / methods
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Excitatory Amino Acid Agonists / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Excitatory Postsynaptic Potentials / radiation effects
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GTP-Binding Proteins / deficiency
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / metabolism
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Gene Expression Regulation, Developmental / physiology
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In Vitro Techniques
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Mutant Strains
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Models, Neurological
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N-Methylaspartate / pharmacology
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Neural Pathways / metabolism*
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Neuronal Plasticity / genetics
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Neurotransmitter Agents / metabolism*
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Patch-Clamp Techniques / methods
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Somatosensory Cortex / drug effects
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Somatosensory Cortex / growth & development*
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Somatosensory Cortex / metabolism*
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Synapsins / metabolism
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Thalamus / metabolism*
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Time Factors
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
Substances
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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Neurotransmitter Agents
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Rims1 protein, mouse
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Synapsins
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N-Methylaspartate
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Dizocilpine Maleate
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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GTP-Binding Proteins
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Adenylyl Cyclases
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adenylyl cyclase 1
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Calcium