title: Thalamic adenylyl cyclase 1 is required for barrel formation in the somatosensory cortex.
abstract: Cyclic 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.
authors: 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.
authors: A
authors: A
authors: Suzuki
authors: Department of Anatomy and Cell Biology, National Taiwan University, Taipei, Taiwan.
authors: L-J
authors: LJ
authors: Lee
authors: Laboratory for Behavioral Genetics, RIKEN Brain Science (BSI) Institute, Wako, Saitama 351-0198, Japan.
authors: Y
authors: Y
authors: Hayashi
authors: Perinatal Institute, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
authors: L
authors: L
authors: Muglia
authors: Laboratory for Behavioral Genetics, RIKEN Brain Science (BSI) Institute, Wako, Saitama 351-0198, Japan.
authors: S
authors: S
authors: Itohara
authors: Department of Anatomy and Neurobiology, University of Maryland, Baltimore, MD 21201-1075, USA.
authors: R S
authors: RS
authors: Erzurumlu
authors: 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. Electronic address: tiwasato@nig.ac.jp.
authors: T
authors: T
authors: Iwasato
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000502:physiology; D007150:Immunohistochemistry; D018345:Mice, Knockout; D056347:Neuroanatomical Tract-Tracing Techniques; D009473:Neuronal Plasticity / Q000502:physiology; D013003:Somatosensory Cortex / Q000254:growth & development* / Q000502:physiology; D013788:Thalamus / Q000254:growth & development / Q000502:physiology*; D014738:Vibrissae / Q000502:physiology
chemical_list: D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1
keywords: Cre/loxP system; conditional knockout; mouse; neuronal circuit; refinement; somatosensory system
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