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.SIGNIFICANCE STATEMENT 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.
- Keywords
- Neurod1 mutation, auditory pathway, cochlear nucleus, inferior colliculus, plasticity, sensory topographical map,
- MeSH
- Behavior, Animal physiology MeSH
- Inferior Colliculi anatomy & histology physiology MeSH
- Spiral Ganglion cytology physiology MeSH
- Brain Mapping MeSH
- Mesencephalon embryology physiology MeSH
- Mice, Knockout MeSH
- Mice MeSH
- Cochlear Nucleus anatomy & histology physiology MeSH
- Hearing physiology MeSH
- Auditory Perception genetics physiology MeSH
- Pregnancy MeSH
- Basic Helix-Loop-Helix Transcription Factors genetics physiology MeSH
- Reflex, Startle genetics physiology MeSH
- Vestibule, Labyrinth anatomy & histology physiology MeSH
- Pitch Perception physiology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Names of Substances
- Neurod1 protein, mouse MeSH Browser
- Basic Helix-Loop-Helix Transcription Factors MeSH
The aim of this paper was to summarise knowledge of IL-22 involvement in multiple sclerosis (MS) and the possible link between IL-22 and two transcription factors - AHR and c-Maf. The conclusion is that despite numerous studies, the exact role of IL-22 in the pathogenesis of MS is still unknown. The expression and function of c-Maf in MS have not been studied. It seems that the functions of c-Maf and AHR are at least partly connected with IL-22, as both directly or indirectly influence the regulation of IL-22 expression. This possible connection has never been studied in MS.
- Keywords
- AHR, EAE, IL-22, c-Maf, multiple sclerosis, transcription factors,
- MeSH
- Adaptor Proteins, Signal Transducing physiology MeSH
- Interleukin-22 MeSH
- Interleukins physiology MeSH
- Humans MeSH
- Receptors, Aryl Hydrocarbon physiology MeSH
- Multiple Sclerosis etiology MeSH
- Basic Helix-Loop-Helix Transcription Factors physiology MeSH
- Transcription Factors physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Adaptor Proteins, Signal Transducing MeSH
- AHR protein, human MeSH Browser
- CMIP protein, human MeSH Browser
- Interleukins MeSH
- Receptors, Aryl Hydrocarbon MeSH
- Basic Helix-Loop-Helix Transcription Factors MeSH
- Transcription Factors MeSH