Journal
NEURON
Volume 82, Issue 4, Pages 822-835Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2014.04.001
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Funding
- US National Institute on Deafness and Other Communication Disorders [04199, 06258]
- NIH [T32 NS007433]
- National Science Foundation IGERT [DGE 0549352]
- National Institute on Deafness and Other Communication Disorders Institutional Training grant [T32 DC011499]
- Pennsylvania Lions Hearing Research Foundation
- Deutsche Forschungsgemeinschaft [Ru 390/19-1, GK 1097]
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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 alpha 9 subunit of nicotinic acetylcholine receptors (alpha 9 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.
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