Journal article
Functional role of neurotrophin-3 in synapse regeneration by spiral ganglion neurons on inner hair cells after excitotoxic trauma in vitro
The Journal of neuroscience, Vol.31(21), pp.7938-7949
05/25/2011
DOI: 10.1523/JNEUROSCI.1434-10.2011
PMCID: PMC3132175
PMID: 21613508
Abstract
Spiral ganglion neurons (SGNs) are postsynaptic to hair cells and project to the brainstem. The inner hair cell (IHC) to SGN synapse is susceptible to glutamate excitotoxicity and to acoustic trauma, with potentially adverse consequences to long-term SGN survival. We used a cochlear explant culture from P6 rat pups consisting of a portion of organ of Corti maintained intact with the corresponding portion of spiral ganglion to investigate excitotoxic damage to IHC-SGN synapses in vitro. The normal innervation pattern is preserved in vitro. Brief treatment with NMDA and kainate results in loss of IHC-SGN synapses and degeneration of the distal type 1 SGN peripheral axons, mimicking damage to SGN peripheral axons caused by excitotoxicity or noise in vivo. The number of IHC presynaptic ribbons is not significantly altered. Reinnervation of IHCs occurs and regenerating axons remain restricted to the IHC row. However, the number of postsynaptic densities (PSDs) does not fully recover and not all axons regrow to the IHCs. Addition of either neurotrophin-3 (NT-3) or BDNF increases axon growth and synaptogenesis. Selective blockade of endogenous NT-3 signaling with TrkC-IgG reduced regeneration of axons and PSDs, but TrkB-IgG, which blocks BDNF, has no such effect, indicating that endogenous NT-3 is necessary for SGN axon growth and synaptogenesis. Remarkably, TrkC-IgG reduced axon growth and synaptogenesis even in the presence of BDNF, indicating that endogenous NT-3 has a distinctive role, not mimicked by BDNF, in promoting SGN axon growth in the organ of Corti and synaptogenesis on IHCs.
Details
- Title: Subtitle
- Functional role of neurotrophin-3 in synapse regeneration by spiral ganglion neurons on inner hair cells after excitotoxic trauma in vitro
- Creators
- Qiong Wang - Department of Biology, University of Iowa, Iowa City, Iowa 52242, USASteven H Green
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.31(21), pp.7938-7949
- DOI
- 10.1523/JNEUROSCI.1434-10.2011
- PMID
- 21613508
- PMCID
- PMC3132175
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Grant note
- R01 DC002961-15 / NIDCD NIH HHS R01 DC02961 / NIDCD NIH HHS P30 DC010362 / NIDCD NIH HHS R01 DC002961 / NIDCD NIH HHS P30 DC010362-02 / NIDCD NIH HHS R01 DC009405 / NIDCD NIH HHS
- Language
- English
- Date published
- 05/25/2011
- Academic Unit
- Biology; Otolaryngology
- Record Identifier
- 9984217533802771
Metrics
14 Record Views