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Loss of auditory activity modifies the location of potassium channel KCNQ5 in auditory brainstem neurons.

Caminos E, Garcia-Pino E, Juiz JM - J. Neurosci. Res. (2014)

Bottom Line: The results were comparable after intracochlear TTX injection, which drastically reduced KCNQ5 immunostaining in MNTB calyces and increased immunolabeling in VCN cell bodies.Endbulbs of Held in the VCN also showed diminished KCNQ5 labeling after intracochlear TTX injection.These results show that peripheral activity from auditory nerve afferents is necessary to maintain the subcellular distribution of KCNQ5 in synaptic endings of the auditory brainstem.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigación en Discapacidades Neurológicas (IDINE), Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, Spain.

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Effects of unilateral TTX injection into the cochlea on KCNQ5 immunoreactivity in the auditory brainstem. A: Representative ABRs to a 16-kHz tone-burst stimulus of an adult rat collected before and after TTX injection into the left bulla. ABRs to the 16-kHz tone stimulus delivered to the left ear were recorded from the left side before TTX injection. After TTX injection, ABRs were eliminated. After stimulation of the contralateral side, waves were present, though attenuated, and thresholds were higher. Sound intensity is indicated in dB SPL. Arrows indicate the start of the stimulus. B–E: Micrographs showing KCNQ5 immunoreactivity in the AVCN (B,C) and the MNTB (D,E) after the unilateral TTX injection. In the ipsilateral AVCN, immunoreactive synaptic endings disappeared around cell bodies, but cell bodies became intensely immunoreactive (B). In the contralateral AVCN of the TTX-treated animals, immunolabeling around the AVCN neurons is observed (C), as seen in the unmanipulated animals and in the vehicle-injected rats (distilled water). The MNTB on the ipsilateral side of the TTX injection shows the abundant immunoreactive synaptic endings surrounding MNTB neurons (D). The contralateral MNTB exhibits the areas where KCNQ5 immunoreactivity disappeared from endings (arrows; E). F: Representative histogram shows the number of immunostained pixels counted on coronal sections of the MNTB (mean ± SD). Note the significant difference between the contralateral side of one animal injected with TTX compared with its ipsilateral side, the unmanipulated animal, and the vehicle-treated control rats. ***P < 0.001. TTX-ipsi, ipsilateral side to TTX injection; TTX-contra, contralateral side to the TTX injection. Scale bar = 20 µm. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]
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fig05: Effects of unilateral TTX injection into the cochlea on KCNQ5 immunoreactivity in the auditory brainstem. A: Representative ABRs to a 16-kHz tone-burst stimulus of an adult rat collected before and after TTX injection into the left bulla. ABRs to the 16-kHz tone stimulus delivered to the left ear were recorded from the left side before TTX injection. After TTX injection, ABRs were eliminated. After stimulation of the contralateral side, waves were present, though attenuated, and thresholds were higher. Sound intensity is indicated in dB SPL. Arrows indicate the start of the stimulus. B–E: Micrographs showing KCNQ5 immunoreactivity in the AVCN (B,C) and the MNTB (D,E) after the unilateral TTX injection. In the ipsilateral AVCN, immunoreactive synaptic endings disappeared around cell bodies, but cell bodies became intensely immunoreactive (B). In the contralateral AVCN of the TTX-treated animals, immunolabeling around the AVCN neurons is observed (C), as seen in the unmanipulated animals and in the vehicle-injected rats (distilled water). The MNTB on the ipsilateral side of the TTX injection shows the abundant immunoreactive synaptic endings surrounding MNTB neurons (D). The contralateral MNTB exhibits the areas where KCNQ5 immunoreactivity disappeared from endings (arrows; E). F: Representative histogram shows the number of immunostained pixels counted on coronal sections of the MNTB (mean ± SD). Note the significant difference between the contralateral side of one animal injected with TTX compared with its ipsilateral side, the unmanipulated animal, and the vehicle-treated control rats. ***P < 0.001. TTX-ipsi, ipsilateral side to TTX injection; TTX-contra, contralateral side to the TTX injection. Scale bar = 20 µm. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Mentions: The unilateral TTX injections in the left cochlea resulted in the complete elimination of normal ABR waves after ipsilateral stimulation. Stimulation of the contralateral ear resulted in a slight but not statistically significant increase in the auditory thresholds as well as a modest attenuation of wave amplitudes, particularly in waves III and IV (Fig. 5A). These results support the conclusion that TTX application blocks central auditory responses to sound by blocking auditory nerve activity.


Loss of auditory activity modifies the location of potassium channel KCNQ5 in auditory brainstem neurons.

Caminos E, Garcia-Pino E, Juiz JM - J. Neurosci. Res. (2014)

Effects of unilateral TTX injection into the cochlea on KCNQ5 immunoreactivity in the auditory brainstem. A: Representative ABRs to a 16-kHz tone-burst stimulus of an adult rat collected before and after TTX injection into the left bulla. ABRs to the 16-kHz tone stimulus delivered to the left ear were recorded from the left side before TTX injection. After TTX injection, ABRs were eliminated. After stimulation of the contralateral side, waves were present, though attenuated, and thresholds were higher. Sound intensity is indicated in dB SPL. Arrows indicate the start of the stimulus. B–E: Micrographs showing KCNQ5 immunoreactivity in the AVCN (B,C) and the MNTB (D,E) after the unilateral TTX injection. In the ipsilateral AVCN, immunoreactive synaptic endings disappeared around cell bodies, but cell bodies became intensely immunoreactive (B). In the contralateral AVCN of the TTX-treated animals, immunolabeling around the AVCN neurons is observed (C), as seen in the unmanipulated animals and in the vehicle-injected rats (distilled water). The MNTB on the ipsilateral side of the TTX injection shows the abundant immunoreactive synaptic endings surrounding MNTB neurons (D). The contralateral MNTB exhibits the areas where KCNQ5 immunoreactivity disappeared from endings (arrows; E). F: Representative histogram shows the number of immunostained pixels counted on coronal sections of the MNTB (mean ± SD). Note the significant difference between the contralateral side of one animal injected with TTX compared with its ipsilateral side, the unmanipulated animal, and the vehicle-treated control rats. ***P < 0.001. TTX-ipsi, ipsilateral side to TTX injection; TTX-contra, contralateral side to the TTX injection. Scale bar = 20 µm. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]
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Related In: Results  -  Collection

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fig05: Effects of unilateral TTX injection into the cochlea on KCNQ5 immunoreactivity in the auditory brainstem. A: Representative ABRs to a 16-kHz tone-burst stimulus of an adult rat collected before and after TTX injection into the left bulla. ABRs to the 16-kHz tone stimulus delivered to the left ear were recorded from the left side before TTX injection. After TTX injection, ABRs were eliminated. After stimulation of the contralateral side, waves were present, though attenuated, and thresholds were higher. Sound intensity is indicated in dB SPL. Arrows indicate the start of the stimulus. B–E: Micrographs showing KCNQ5 immunoreactivity in the AVCN (B,C) and the MNTB (D,E) after the unilateral TTX injection. In the ipsilateral AVCN, immunoreactive synaptic endings disappeared around cell bodies, but cell bodies became intensely immunoreactive (B). In the contralateral AVCN of the TTX-treated animals, immunolabeling around the AVCN neurons is observed (C), as seen in the unmanipulated animals and in the vehicle-injected rats (distilled water). The MNTB on the ipsilateral side of the TTX injection shows the abundant immunoreactive synaptic endings surrounding MNTB neurons (D). The contralateral MNTB exhibits the areas where KCNQ5 immunoreactivity disappeared from endings (arrows; E). F: Representative histogram shows the number of immunostained pixels counted on coronal sections of the MNTB (mean ± SD). Note the significant difference between the contralateral side of one animal injected with TTX compared with its ipsilateral side, the unmanipulated animal, and the vehicle-treated control rats. ***P < 0.001. TTX-ipsi, ipsilateral side to TTX injection; TTX-contra, contralateral side to the TTX injection. Scale bar = 20 µm. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]
Mentions: The unilateral TTX injections in the left cochlea resulted in the complete elimination of normal ABR waves after ipsilateral stimulation. Stimulation of the contralateral ear resulted in a slight but not statistically significant increase in the auditory thresholds as well as a modest attenuation of wave amplitudes, particularly in waves III and IV (Fig. 5A). These results support the conclusion that TTX application blocks central auditory responses to sound by blocking auditory nerve activity.

Bottom Line: The results were comparable after intracochlear TTX injection, which drastically reduced KCNQ5 immunostaining in MNTB calyces and increased immunolabeling in VCN cell bodies.Endbulbs of Held in the VCN also showed diminished KCNQ5 labeling after intracochlear TTX injection.These results show that peripheral activity from auditory nerve afferents is necessary to maintain the subcellular distribution of KCNQ5 in synaptic endings of the auditory brainstem.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigación en Discapacidades Neurológicas (IDINE), Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, Spain.

Show MeSH
Related in: MedlinePlus