Cholinergic efferent synaptic transmission regulates the maturation of auditory hair cell ribbon synapses
Spontaneous electrical activity generated by developing sensory cells and neurons is crucial for the maturation of neural circuits. The full maturation of mammalian auditory inner hair cells (IHCs) depends on patterns of spontaneous action potentials during a 'critical period' of developme...
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todo:paper_20462441_v3_nNOV_p_Johnson2023-10-03T16:38:41Z Cholinergic efferent synaptic transmission regulates the maturation of auditory hair cell ribbon synapses Johnson, S.L. Wedemeyer, C. Vetter, D.E. Adachi, R. Holley, M.C. Elgoyhen, A.B. Marcotti, W. Calcium current Cochlea Development Efferent system Exocytosis Hair cell Chrna9 protein, mouse nicotinic receptor synaptotagmin II Syt2 protein, mouse action potential animal article cochlea genetics hair cell knockout mouse motoneuron mouse physiology stereocilium synapse synaptic transmission Action Potentials Animals Cochlea Hair Cells, Auditory, Inner Mice Mice, Knockout Motor Neurons Receptors, Nicotinic Stereocilia Synapses Synaptic Transmission Synaptotagmin II Spontaneous electrical activity generated by developing sensory cells and neurons is crucial for the maturation of neural circuits. The full maturation of mammalian auditory inner hair cells (IHCs) depends on patterns of spontaneous action potentials during a 'critical period' of development. The intrinsic spiking activity of IHCs can be modulated by inhibitory input from cholinergic efferent fibres descending from the brainstem, which transiently innervate immature IHCs. However, it remains unknown whether this transient efferent input to developing IHCs is required for their functional maturation. We used a mouse model that lacks the a9-nicotinic acetylcholine receptor subunit (a9nAChR) in IHCs and another lacking synaptotagmin-2 in the efferent terminals to remove or reduce efferent input to IHCs, respectively. We found that the efferent system is required for the developmental linearization of the Ca2p-sensitivity of vesicle fusion at IHC ribbon synapses, without affecting their general cell development. This provides the first direct evidence that the efferent system, by modulating IHC electrical activity, is required for the maturation of the IHC synaptic machinery. The central control of sensory cell development is unique among sensory systems. © 2013 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_20462441_v3_nNOV_p_Johnson |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Calcium current Cochlea Development Efferent system Exocytosis Hair cell Chrna9 protein, mouse nicotinic receptor synaptotagmin II Syt2 protein, mouse action potential animal article cochlea genetics hair cell knockout mouse motoneuron mouse physiology stereocilium synapse synaptic transmission Action Potentials Animals Cochlea Hair Cells, Auditory, Inner Mice Mice, Knockout Motor Neurons Receptors, Nicotinic Stereocilia Synapses Synaptic Transmission Synaptotagmin II |
| spellingShingle |
Calcium current Cochlea Development Efferent system Exocytosis Hair cell Chrna9 protein, mouse nicotinic receptor synaptotagmin II Syt2 protein, mouse action potential animal article cochlea genetics hair cell knockout mouse motoneuron mouse physiology stereocilium synapse synaptic transmission Action Potentials Animals Cochlea Hair Cells, Auditory, Inner Mice Mice, Knockout Motor Neurons Receptors, Nicotinic Stereocilia Synapses Synaptic Transmission Synaptotagmin II Johnson, S.L. Wedemeyer, C. Vetter, D.E. Adachi, R. Holley, M.C. Elgoyhen, A.B. Marcotti, W. Cholinergic efferent synaptic transmission regulates the maturation of auditory hair cell ribbon synapses |
| topic_facet |
Calcium current Cochlea Development Efferent system Exocytosis Hair cell Chrna9 protein, mouse nicotinic receptor synaptotagmin II Syt2 protein, mouse action potential animal article cochlea genetics hair cell knockout mouse motoneuron mouse physiology stereocilium synapse synaptic transmission Action Potentials Animals Cochlea Hair Cells, Auditory, Inner Mice Mice, Knockout Motor Neurons Receptors, Nicotinic Stereocilia Synapses Synaptic Transmission Synaptotagmin II |
| description |
Spontaneous electrical activity generated by developing sensory cells and neurons is crucial for the maturation of neural circuits. The full maturation of mammalian auditory inner hair cells (IHCs) depends on patterns of spontaneous action potentials during a 'critical period' of development. The intrinsic spiking activity of IHCs can be modulated by inhibitory input from cholinergic efferent fibres descending from the brainstem, which transiently innervate immature IHCs. However, it remains unknown whether this transient efferent input to developing IHCs is required for their functional maturation. We used a mouse model that lacks the a9-nicotinic acetylcholine receptor subunit (a9nAChR) in IHCs and another lacking synaptotagmin-2 in the efferent terminals to remove or reduce efferent input to IHCs, respectively. We found that the efferent system is required for the developmental linearization of the Ca2p-sensitivity of vesicle fusion at IHC ribbon synapses, without affecting their general cell development. This provides the first direct evidence that the efferent system, by modulating IHC electrical activity, is required for the maturation of the IHC synaptic machinery. The central control of sensory cell development is unique among sensory systems. © 2013 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License. |
| format |
JOUR |
| author |
Johnson, S.L. Wedemeyer, C. Vetter, D.E. Adachi, R. Holley, M.C. Elgoyhen, A.B. Marcotti, W. |
| author_facet |
Johnson, S.L. Wedemeyer, C. Vetter, D.E. Adachi, R. Holley, M.C. Elgoyhen, A.B. Marcotti, W. |
| author_sort |
Johnson, S.L. |
| title |
Cholinergic efferent synaptic transmission regulates the maturation of auditory hair cell ribbon synapses |
| title_short |
Cholinergic efferent synaptic transmission regulates the maturation of auditory hair cell ribbon synapses |
| title_full |
Cholinergic efferent synaptic transmission regulates the maturation of auditory hair cell ribbon synapses |
| title_fullStr |
Cholinergic efferent synaptic transmission regulates the maturation of auditory hair cell ribbon synapses |
| title_full_unstemmed |
Cholinergic efferent synaptic transmission regulates the maturation of auditory hair cell ribbon synapses |
| title_sort |
cholinergic efferent synaptic transmission regulates the maturation of auditory hair cell ribbon synapses |
| url |
http://hdl.handle.net/20.500.12110/paper_20462441_v3_nNOV_p_Johnson |
| work_keys_str_mv |
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1807316578553823232 |