• Neuroscience · Apr 2015

    Thalamic adenylyl cyclase 1 is required for barrel formation in the somatosensory cortex.

    • A Suzuki, L-J Lee, Y Hayashi, L Muglia, S Itohara, R S Erzurumlu, and T Iwasato.
    • Division of Neurogenetics, National Institute of Genetics (NIG), Mishima, Shizuoka 411-8540, Japan; Department of Genetics, The Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka 411-8540, Japan.
    • Neuroscience. 2015 Apr 2;290:518-29.

    AbstractCyclic AMP signaling is critical for activity-dependent refinement of neuronal circuits. Global disruption of adenylyl cyclase 1 (AC1), the major calcium/calmodulin-stimulated adenylyl cyclase in the brain, impairs formation of whisker-related discrete neural modules (the barrels) in cortical layer 4 in mice. Since AC1 is expressed both in the thalamus and the neocortex, the question of whether pre- or postsynaptic (or both) AC1 plays a role in barrel formation has emerged. Previously, we generated cortex-specific AC1 knockout (Cx-AC1KO) mice and found that these animals develop histologically normal barrels, suggesting a potentially more prominent role for thalamic AC1 in barrel formation. To determine this, we generated three new lines of mice: one in which AC1 is disrupted in nearly half of the thalamic ventrobasal nucleus cells in addition to the cortical excitatory neurons (Cx/pTh-AC1KO mouse), and another in which AC1 is disrupted in the thalamus but not in the cortex or brainstem nuclei of the somatosensory system (Th-AC1KO mouse). Cx/pTh-AC1KO mice show severe deficits in barrel formation. Th-AC1KO mice show even more severe disruption in barrel patterning. In these two lines, single thalamocortical (TC) axon labeling revealed a larger lateral extent of TC axons in layer 4 compared to controls. In the third line, all calcium-stimulated adenylyl cyclases (both AC1 and AC8) are deleted in cortical excitatory neurons. These mice have normal barrels. Taken together, these results indicate that thalamic AC1 plays a major role in patterning and refinement of the mouse TC circuitry.Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

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