Fewer GABAergic interneurons, heightened anxiety and decreased high-frequency electroencephalogram components in Bronx waltzer mice, a model of hereditary deafness

The homozygous Bronx waltzer mutation (bv/bv) results in the degeneration of most but not all of the primary auditory receptors, the inner hair cells and their afferent neurons, and leads to perceptive deafness. However, the influence of the mutation on the central nervous system (CNS) remains largely unclear. In this study, we have conducted behavioral, morphological and electrophysiological investigations to clarify the CNS dysfunction in bv/bv mice. These mutant mice exhibited heightened levels of anxiety with normal levels of motor activity. Immunohistochemical analysis revealed a significant reduction in parvalbumin-containing GABAergic interneurons in the anterior cingulate, somatosensory and auditory cortices of bv/bv mice. The current results suggest that interneuron development may be disrupted in the bv/bv cerebrum. Moreover, the high-frequency electroencephalogram components of the cortical activity, including the frequency range containing high gamma, were markedly decreased in bv/bv mice compared with controls, probably indicating a disturbance in cortical inhibitory function. Together, these results suggest that the cortical development of interneurons and their electrophysiological profiles are altered in bv/bv mice. We propose that these novel phenotypes identified in bv/bv mice provide new perspectives on the basic neuronal mechanisms of developmental disorders. (c) 2010 Elsevier B.V. All rights reserved.