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

Neuroscience. 2015 Apr 2;290:518-29. doi: 10.1016/j.neuroscience.2015.01.043. Epub 2015 Jan 30.

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.

Keywords: Cre/loxP system; conditional knockout; mouse; neuronal circuit; refinement; somatosensory system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / genetics
  • Adenylyl Cyclases / metabolism*
  • Animals
  • Axons / physiology
  • Immunohistochemistry
  • Mice, Knockout
  • Neuroanatomical Tract-Tracing Techniques
  • Neuronal Plasticity / physiology
  • Somatosensory Cortex / growth & development*
  • Somatosensory Cortex / physiology
  • Thalamus / growth & development
  • Thalamus / physiology*
  • Vibrissae / physiology

Substances

  • Adenylyl Cyclases
  • adenylyl cyclase 1