Journal article
Neurod1 Is Essential for the Primary Tonotopic Organization and Related Auditory Information Processing in the Midbrain
The Journal of neuroscience, Vol.39(6), pp.984-1004
02/06/2019
DOI: 10.1523/JNEUROSCI.2557-18.2018
PMCID: PMC6363931
PMID: 30541910
Abstract
Hearing depends on extracting frequency, intensity, and temporal properties from sound to generate an auditory map for acoustical signal processing. How physiology intersects with molecular specification to fine tune the developing properties of the auditory system that enable these aspects remains unclear. We made a novel conditional deletion model that eliminates the transcription factor NEUROD1 exclusively in the ear. These mice (both sexes) develop a truncated frequency range with no neuroanatomically recognizable mapping of spiral ganglion neurons onto distinct locations in the cochlea nor a cochleotopic map presenting topographically discrete projections to the cochlear nuclei. The disorganized primary cochleotopic map alters tuning properties of the inferior colliculus units, which display abnormal frequency, intensity, and temporal sound coding. At the behavioral level, animals show alterations in the acoustic startle response, consistent with altered neuroanatomical and physiological properties. We demonstrate that absence of the primary afferent topology during embryonic development leads to dysfunctional tonotopy of the auditory system. Such effects have never been investigated in other sensory systems because of the lack of comparable single gene mutation models.
All sensory systems form a topographical map of neuronal projections from peripheral sensory organs to the brain. Neuronal projections in the auditory pathway are cochleotopically organized, providing a tonotopic map of sound frequencies. Primary sensory maps typically arise by molecular cues, requiring physiological refinements. Past work has demonstrated physiologic plasticity in many senses without ever molecularly undoing the specific mapping of an entire primary sensory projection. We genetically manipulated primary auditory neurons to generate a scrambled cochleotopic projection. Eliminating tonotopic representation to auditory nuclei demonstrates the inability of physiological processes to restore a tonotopic presentation of sound in the midbrain. Our data provide the first insights into the limits of physiology-mediated brainstem plasticity during the development of the auditory system.
Details
- Title: Subtitle
- Neurod1 Is Essential for the Primary Tonotopic Organization and Related Auditory Information Processing in the Midbrain
- Creators
- Iva Macova - Faculty of Science, Charles University, Prague, Czechia 12843Kateryna Pysanenko - Institute of Experimental Medicine CAS, Prague, Czechia 14220Tetyana Chumak - Institute of Experimental Medicine CAS, Prague, Czechia 14220Martina Dvorakova - Faculty of Science, Charles University, Prague, Czechia 12843Romana Bohuslavova - Institute of Biotechnology CAS, Vestec, Czechia 25250Josef Syka - Institute of Experimental Medicine CAS, Prague, Czechia 14220Bernd Fritzsch - Department of Biology, University of Iowa, Iowa City, Iowa 52242, and Gabriela.Pavlinkova@ibt.cas.cz bernd-fritzsch@uiowa.eduGabriela Pavlinkova - Institute of Biotechnology CAS, Vestec, Czechia 25250, Gabriela.Pavlinkova@ibt.cas.cz bernd-fritzsch@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.39(6), pp.984-1004
- DOI
- 10.1523/JNEUROSCI.2557-18.2018
- PMID
- 30541910
- PMCID
- PMC6363931
- NLM abbreviation
- J Neurosci
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Publisher
- United States
- Grant note
- R01 AG060504 / NIA NIH HHS
- Language
- English
- Date published
- 02/06/2019
- Academic Unit
- Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984070653202771
Metrics
25 Record Views