Hox2 Genes Are Required for Tonotopic Map Precision and Sound Discrimination in the Mouse Auditory Brainstem

Publication date: 3 January 2017
Source:Cell Reports, Volume 18, Issue 1
Author(s): Kajari Karmakar, Yuichi Narita, Jonathan Fadok, Sebastien Ducret, Alberto Loche, Taro Kitazawa, Christel Genoud, Thomas Di Meglio, Raphael Thierry, Joao Bacelo, Andreas Lüthi, Filippo M. Rijli
Tonotopy is a hallmark of auditory pathways and provides the basis for sound discrimination. Little is known about the involvement of transcription factors in brainstem cochlear neurons orchestrating the tonotopic precision of pre-synaptic input. We found that in the absence of Hoxa2 and Hoxb2 function in Atoh1-derived glutamatergic bushy cells of the anterior ventral cochlear nucleus, broad input topography and sound transmission were largely preserved. However, fine-scale synaptic refinement and sharpening of isofrequency bands of cochlear neuron activation upon pure tone stimulation were impaired in Hox2 mutants, resulting in defective sound-frequency discrimination in behavioral tests. These results establish a role for Hox factors in tonotopic refinement of connectivity and in ensuring the precision of sound transmission in the mammalian auditory circuit.

Graphical abstract

Teaser

Karmakar et al. find that the Hoxa2 and Hoxb2 transcription factors are required in mouse brainstem cochlear neurons for the tonotopic maturation of synaptic targeting from their peripheral auditory afferents and for the precision of sound discrimination in adult mice.


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