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GC-B Deficient Mice With Axon Bifurcation Loss Exhibit Compromised Auditory Processing

Sensory axon T-like branching (bifurcation) in neurons from dorsal root ganglia and cranial sensory ganglia depends on the molecular signaling cascade involving the secreted factor C-type natriuretic peptide, the natriuretic peptide receptor guanylyl cyclase B (GC-B; also known as Npr2) and cGMP-dep...

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Autores principales: Wolter, Steffen, Möhrle, Dorit, Schmidt, Hannes, Pfeiffer, Sylvia, Zelle, Dennis, Eckert, Philipp, Krämer, Michael, Feil, Robert, Pilz, Peter K. D., Knipper, Marlies, Rüttiger, Lukas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152484/
https://www.ncbi.nlm.nih.gov/pubmed/30275816
http://dx.doi.org/10.3389/fncir.2018.00065
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author Wolter, Steffen
Möhrle, Dorit
Schmidt, Hannes
Pfeiffer, Sylvia
Zelle, Dennis
Eckert, Philipp
Krämer, Michael
Feil, Robert
Pilz, Peter K. D.
Knipper, Marlies
Rüttiger, Lukas
author_facet Wolter, Steffen
Möhrle, Dorit
Schmidt, Hannes
Pfeiffer, Sylvia
Zelle, Dennis
Eckert, Philipp
Krämer, Michael
Feil, Robert
Pilz, Peter K. D.
Knipper, Marlies
Rüttiger, Lukas
author_sort Wolter, Steffen
collection PubMed
description Sensory axon T-like branching (bifurcation) in neurons from dorsal root ganglia and cranial sensory ganglia depends on the molecular signaling cascade involving the secreted factor C-type natriuretic peptide, the natriuretic peptide receptor guanylyl cyclase B (GC-B; also known as Npr2) and cGMP-dependent protein kinase I (cGKI, also known as PKGI). The bifurcation of cranial nerves is suggested to be important for information processing by second-order neurons in the hindbrain or spinal cord. Indeed, mice with a spontaneous GC-B loss of function mutation (Npr2(cn/cn)) display an impaired bifurcation of auditory nerve (AN) fibers. However, these mice did not show any obvious sign of impaired basal hearing. Here, we demonstrate that mice with a targeted inactivation of the GC-B gene (Npr2(lacZ/lacZ), GC-B KO mice) show an elevation of audiometric thresholds. In the inner ear, the cochlear hair cells in GC-B KO mice were nevertheless similar to those from wild type mice, justified by the typical expression of functionally relevant marker proteins. However, efferent cholinergic feedback to inner and outer hair cells was reduced in GC-B KO mice, linked to very likely reduced rapid efferent feedback. Sound-evoked AN responses of GC-B KO mice were elevated, a feature that is known to occur when the efferent axo-dendritic feedback on AN is compromised. Furthermore, late sound-evoked brainstem responses were significantly delayed in GC-B KO mice. This delay in sound response was accompanied by a weaker sensitivity of the auditory steady state response to amplitude-modulated sound stimuli. Finally, the acoustic startle response (ASR) – one of the fastest auditory responses – and the prepulse inhibition of the ASR indicated significant changes in temporal precision of auditory processing. These findings suggest that GC-B-controlled axon bifurcation of spiral ganglion neurons is important for proper activation of second-order neurons in the hindbrain and is a prerequisite for proper temporal auditory processing likely by establishing accurate efferent top-down control circuits. These data hypothesize that the bifurcation pattern of cranial nerves is important to shape spatial and temporal information processing for sensory feedback control.
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spelling pubmed-61524842018-10-01 GC-B Deficient Mice With Axon Bifurcation Loss Exhibit Compromised Auditory Processing Wolter, Steffen Möhrle, Dorit Schmidt, Hannes Pfeiffer, Sylvia Zelle, Dennis Eckert, Philipp Krämer, Michael Feil, Robert Pilz, Peter K. D. Knipper, Marlies Rüttiger, Lukas Front Neural Circuits Neuroscience Sensory axon T-like branching (bifurcation) in neurons from dorsal root ganglia and cranial sensory ganglia depends on the molecular signaling cascade involving the secreted factor C-type natriuretic peptide, the natriuretic peptide receptor guanylyl cyclase B (GC-B; also known as Npr2) and cGMP-dependent protein kinase I (cGKI, also known as PKGI). The bifurcation of cranial nerves is suggested to be important for information processing by second-order neurons in the hindbrain or spinal cord. Indeed, mice with a spontaneous GC-B loss of function mutation (Npr2(cn/cn)) display an impaired bifurcation of auditory nerve (AN) fibers. However, these mice did not show any obvious sign of impaired basal hearing. Here, we demonstrate that mice with a targeted inactivation of the GC-B gene (Npr2(lacZ/lacZ), GC-B KO mice) show an elevation of audiometric thresholds. In the inner ear, the cochlear hair cells in GC-B KO mice were nevertheless similar to those from wild type mice, justified by the typical expression of functionally relevant marker proteins. However, efferent cholinergic feedback to inner and outer hair cells was reduced in GC-B KO mice, linked to very likely reduced rapid efferent feedback. Sound-evoked AN responses of GC-B KO mice were elevated, a feature that is known to occur when the efferent axo-dendritic feedback on AN is compromised. Furthermore, late sound-evoked brainstem responses were significantly delayed in GC-B KO mice. This delay in sound response was accompanied by a weaker sensitivity of the auditory steady state response to amplitude-modulated sound stimuli. Finally, the acoustic startle response (ASR) – one of the fastest auditory responses – and the prepulse inhibition of the ASR indicated significant changes in temporal precision of auditory processing. These findings suggest that GC-B-controlled axon bifurcation of spiral ganglion neurons is important for proper activation of second-order neurons in the hindbrain and is a prerequisite for proper temporal auditory processing likely by establishing accurate efferent top-down control circuits. These data hypothesize that the bifurcation pattern of cranial nerves is important to shape spatial and temporal information processing for sensory feedback control. Frontiers Media S.A. 2018-08-29 /pmc/articles/PMC6152484/ /pubmed/30275816 http://dx.doi.org/10.3389/fncir.2018.00065 Text en Copyright © 2018 Wolter, Möhrle, Schmidt, Pfeiffer, Zelle, Eckert, Krämer, Feil, Pilz, Knipper and Rüttiger. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Wolter, Steffen
Möhrle, Dorit
Schmidt, Hannes
Pfeiffer, Sylvia
Zelle, Dennis
Eckert, Philipp
Krämer, Michael
Feil, Robert
Pilz, Peter K. D.
Knipper, Marlies
Rüttiger, Lukas
GC-B Deficient Mice With Axon Bifurcation Loss Exhibit Compromised Auditory Processing
title GC-B Deficient Mice With Axon Bifurcation Loss Exhibit Compromised Auditory Processing
title_full GC-B Deficient Mice With Axon Bifurcation Loss Exhibit Compromised Auditory Processing
title_fullStr GC-B Deficient Mice With Axon Bifurcation Loss Exhibit Compromised Auditory Processing
title_full_unstemmed GC-B Deficient Mice With Axon Bifurcation Loss Exhibit Compromised Auditory Processing
title_short GC-B Deficient Mice With Axon Bifurcation Loss Exhibit Compromised Auditory Processing
title_sort gc-b deficient mice with axon bifurcation loss exhibit compromised auditory processing
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152484/
https://www.ncbi.nlm.nih.gov/pubmed/30275816
http://dx.doi.org/10.3389/fncir.2018.00065
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