Deletion of nicotinic α9 subunit alters spontaneous activity in auditory system
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α9 KO mice have impaired refinement of an inhibitory tonotopic map
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Imprecise tonotopy in α9 KO mice is present on functional and structural levels
Summary
Patterned spontaneous activity is a hallmark of developing sensory systems. In the auditory system, rhythmic bursts of spontaneous activity are generated in cochlear hair cells and propagated along central auditory pathways. The role of these activity patterns in the development of central auditory circuits has remained speculative. Here we demonstrate that blocking efferent cholinergic neurotransmission to developing hair cells in mice that lack the α9 subunit of nicotinic acetylcholine receptors (α9 KO mice) altered the temporal fine structure of spontaneous activity without changing activity levels. KO mice showed a severe impairment in the functional and structural sharpening of an inhibitory tonotopic map, as evidenced by deficits in synaptic strengthening and silencing of connections and an absence in axonal pruning. These results provide evidence that the precise temporal pattern of spontaneous activity before hearing onset is crucial for the establishment of precise tonotopy, the major organizing principle of central auditory pathways.
Present address: Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02114, USA
Present address: Department of Physiology, Center for Integrative Neuroscience, University of California San Francisco, San Francisco, CA 94143-0444, USA