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Nitric Oxide Is an Activity-Dependent Regulator of Target Neuron Intrinsic Excitability

Activity-dependent changes in synaptic strength are well established as mediating long-term plasticity underlying learning and memory, but modulation of target neuron excitability could complement changes in synaptic strength and regulate network activity. It is thought that homeostatic mechanisms m...

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Autores principales: Steinert, Joern R., Robinson, Susan W., Tong, Huaxia, Haustein, Martin D., Kopp-Scheinpflug, Cornelia, Forsythe, Ian D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245892/
https://www.ncbi.nlm.nih.gov/pubmed/21791288
http://dx.doi.org/10.1016/j.neuron.2011.05.037
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author Steinert, Joern R.
Robinson, Susan W.
Tong, Huaxia
Haustein, Martin D.
Kopp-Scheinpflug, Cornelia
Forsythe, Ian D.
author_facet Steinert, Joern R.
Robinson, Susan W.
Tong, Huaxia
Haustein, Martin D.
Kopp-Scheinpflug, Cornelia
Forsythe, Ian D.
author_sort Steinert, Joern R.
collection PubMed
description Activity-dependent changes in synaptic strength are well established as mediating long-term plasticity underlying learning and memory, but modulation of target neuron excitability could complement changes in synaptic strength and regulate network activity. It is thought that homeostatic mechanisms match intrinsic excitability to the incoming synaptic drive, but evidence for involvement of voltage-gated conductances is sparse. Here, we show that glutamatergic synaptic activity modulates target neuron excitability and switches the basis of action potential repolarization from Kv3 to Kv2 potassium channel dominance, thereby adjusting neuronal signaling between low and high activity states, respectively. This nitric oxide-mediated signaling dramatically increases Kv2 currents in both the auditory brain stem and hippocampus (>3-fold) transforming synaptic integration and information transmission but with only modest changes in action potential waveform. We conclude that nitric oxide is a homeostatic regulator, tuning neuronal excitability to the recent history of excitatory synaptic inputs over intervals of minutes to hours.
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spelling pubmed-32458922011-12-28 Nitric Oxide Is an Activity-Dependent Regulator of Target Neuron Intrinsic Excitability Steinert, Joern R. Robinson, Susan W. Tong, Huaxia Haustein, Martin D. Kopp-Scheinpflug, Cornelia Forsythe, Ian D. Neuron Article Activity-dependent changes in synaptic strength are well established as mediating long-term plasticity underlying learning and memory, but modulation of target neuron excitability could complement changes in synaptic strength and regulate network activity. It is thought that homeostatic mechanisms match intrinsic excitability to the incoming synaptic drive, but evidence for involvement of voltage-gated conductances is sparse. Here, we show that glutamatergic synaptic activity modulates target neuron excitability and switches the basis of action potential repolarization from Kv3 to Kv2 potassium channel dominance, thereby adjusting neuronal signaling between low and high activity states, respectively. This nitric oxide-mediated signaling dramatically increases Kv2 currents in both the auditory brain stem and hippocampus (>3-fold) transforming synaptic integration and information transmission but with only modest changes in action potential waveform. We conclude that nitric oxide is a homeostatic regulator, tuning neuronal excitability to the recent history of excitatory synaptic inputs over intervals of minutes to hours. Cell Press 2011-07-28 /pmc/articles/PMC3245892/ /pubmed/21791288 http://dx.doi.org/10.1016/j.neuron.2011.05.037 Text en © 2011 ELL & Excerpta Medica. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
spellingShingle Article
Steinert, Joern R.
Robinson, Susan W.
Tong, Huaxia
Haustein, Martin D.
Kopp-Scheinpflug, Cornelia
Forsythe, Ian D.
Nitric Oxide Is an Activity-Dependent Regulator of Target Neuron Intrinsic Excitability
title Nitric Oxide Is an Activity-Dependent Regulator of Target Neuron Intrinsic Excitability
title_full Nitric Oxide Is an Activity-Dependent Regulator of Target Neuron Intrinsic Excitability
title_fullStr Nitric Oxide Is an Activity-Dependent Regulator of Target Neuron Intrinsic Excitability
title_full_unstemmed Nitric Oxide Is an Activity-Dependent Regulator of Target Neuron Intrinsic Excitability
title_short Nitric Oxide Is an Activity-Dependent Regulator of Target Neuron Intrinsic Excitability
title_sort nitric oxide is an activity-dependent regulator of target neuron intrinsic excitability
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245892/
https://www.ncbi.nlm.nih.gov/pubmed/21791288
http://dx.doi.org/10.1016/j.neuron.2011.05.037
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