Nitric Oxide Signaling in the Auditory Pathway

Nitric oxide (NO) is of fundamental importance in regulating immune, cardiovascular, reproductive, neuromuscular, and nervous system function. It is rapidly synthesized and cannot be confined, it is highly reactive, so its lifetime is measured in seconds. These distinctive properties (contrasting wi...

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Main Authors: Conny Kopp-Scheinpflug, Ian D. Forsythe
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-10-01
Series:Frontiers in Neural Circuits
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fncir.2021.759342/full
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author Conny Kopp-Scheinpflug
Ian D. Forsythe
author_facet Conny Kopp-Scheinpflug
Ian D. Forsythe
author_sort Conny Kopp-Scheinpflug
collection DOAJ
description Nitric oxide (NO) is of fundamental importance in regulating immune, cardiovascular, reproductive, neuromuscular, and nervous system function. It is rapidly synthesized and cannot be confined, it is highly reactive, so its lifetime is measured in seconds. These distinctive properties (contrasting with classical neurotransmitters and neuromodulators) give rise to the concept of NO as a “volume transmitter,” where it is generated from an active source, diffuses to interact with proteins and receptors within a sphere of influence or volume, but limited in distance and time by its short half-life. In the auditory system, the neuronal NO-synthetizing enzyme, nNOS, is highly expressed and tightly coupled to postsynaptic calcium influx at excitatory synapses. This provides a powerful activity-dependent control of postsynaptic intrinsic excitability via cGMP generation, protein kinase G activation and modulation of voltage-gated conductances. NO may also regulate vesicle mobility via retrograde signaling. This Mini Review focuses on the auditory system, but highlights general mechanisms by which NO mediates neuronal intrinsic plasticity and synaptic transmission. The dependence of NO generation on synaptic and sound-evoked activity has important local modulatory actions and NO serves as a “volume transmitter” in the auditory brainstem. It also has potentially destructive consequences during intense activity or on spill-over from other NO sources during pathological conditions, when aberrant signaling may interfere with the precisely timed and tonotopically organized auditory system.
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spelling doaj.art-44de22f0a07d40abaf3f99a568fce0892022-12-21T23:32:02ZengFrontiers Media S.A.Frontiers in Neural Circuits1662-51102021-10-011510.3389/fncir.2021.759342759342Nitric Oxide Signaling in the Auditory PathwayConny Kopp-Scheinpflug0Ian D. Forsythe1Neurobiology Laboratory, Division of Neurobiology, Faculty of Biology, Ludwig Maximilian University of Munich, Munich, GermanyAuditory Neurophysiology Laboratory, Department of Neuroscience, Psychology and Behaviour, College of Life Sciences, University of Leicester, Leicester, United KingdomNitric oxide (NO) is of fundamental importance in regulating immune, cardiovascular, reproductive, neuromuscular, and nervous system function. It is rapidly synthesized and cannot be confined, it is highly reactive, so its lifetime is measured in seconds. These distinctive properties (contrasting with classical neurotransmitters and neuromodulators) give rise to the concept of NO as a “volume transmitter,” where it is generated from an active source, diffuses to interact with proteins and receptors within a sphere of influence or volume, but limited in distance and time by its short half-life. In the auditory system, the neuronal NO-synthetizing enzyme, nNOS, is highly expressed and tightly coupled to postsynaptic calcium influx at excitatory synapses. This provides a powerful activity-dependent control of postsynaptic intrinsic excitability via cGMP generation, protein kinase G activation and modulation of voltage-gated conductances. NO may also regulate vesicle mobility via retrograde signaling. This Mini Review focuses on the auditory system, but highlights general mechanisms by which NO mediates neuronal intrinsic plasticity and synaptic transmission. The dependence of NO generation on synaptic and sound-evoked activity has important local modulatory actions and NO serves as a “volume transmitter” in the auditory brainstem. It also has potentially destructive consequences during intense activity or on spill-over from other NO sources during pathological conditions, when aberrant signaling may interfere with the precisely timed and tonotopically organized auditory system.https://www.frontiersin.org/articles/10.3389/fncir.2021.759342/fullauditory processingneuronal excitability and ion channel regulationhearing lossneuronal nitric oxide synthase (nNOS)volume transmissionsynaptic plasticity
spellingShingle Conny Kopp-Scheinpflug
Ian D. Forsythe
Nitric Oxide Signaling in the Auditory Pathway
Frontiers in Neural Circuits
auditory processing
neuronal excitability and ion channel regulation
hearing loss
neuronal nitric oxide synthase (nNOS)
volume transmission
synaptic plasticity
title Nitric Oxide Signaling in the Auditory Pathway
title_full Nitric Oxide Signaling in the Auditory Pathway
title_fullStr Nitric Oxide Signaling in the Auditory Pathway
title_full_unstemmed Nitric Oxide Signaling in the Auditory Pathway
title_short Nitric Oxide Signaling in the Auditory Pathway
title_sort nitric oxide signaling in the auditory pathway
topic auditory processing
neuronal excitability and ion channel regulation
hearing loss
neuronal nitric oxide synthase (nNOS)
volume transmission
synaptic plasticity
url https://www.frontiersin.org/articles/10.3389/fncir.2021.759342/full
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