The precise temporal pattern of prehearing spontaneous activity is necessary for tonotopic map refinement.
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.
Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Center for the Neural Basis of Cognition, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Amanda
A
Clause
Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Center for the Neural Basis of Cognition, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. Electronic address: gkim@phy.ucsf.edu.
Gunsoo
G
Kim
Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, 04103 Leipzig, Germany.
Mandy
M
Sonntag
Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Catherine J C
CJ
Weisz
Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Douglas E
DE
Vetter
Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, 04103 Leipzig, Germany.
Rudolf
R
Rűbsamen
Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Center for the Neural Basis of Cognition, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. Electronic address: kkarl@pitt.edu.
Karl
K
Kandler
D000200:Action Potentials / Q000235:genetics / Q000502:physiology*; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001306:Auditory Pathways / Q000254:growth & development / Q000502:physiology*; D001703:Biophysics; D001931:Brain Mapping; D001933:Brain Stem / Q000166:cytology* / Q000254:growth & development; D004558:Electric Stimulation; D007839:Functional Laterality / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000235:genetics; D009622:Noise; D009847:Olivary Nucleus / Q000166:cytology / Q000254:growth & development; D011978:Receptors, Nicotinic / Q000172:deficiency
C402445:Chrna9 protein, mouse; D011978:Receptors, Nicotinic