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Efficient Integration of Synaptic Events by NMDA Receptors in Three-Dimensional Neuropil

Sustained activation of NMDA receptors (NMDARs) plays an important role in controlling activity of neural circuits in the brain. However, whether this activation reflects the ambient level of excitatory neurotransmitter glutamate in brain tissue or whether it depends mainly on local synaptic dischar...

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Detalles Bibliográficos
Autores principales: Zheng, Kaiyu, Rusakov, Dmitri A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Biophysical Society 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456998/
https://www.ncbi.nlm.nih.gov/pubmed/25992724
http://dx.doi.org/10.1016/j.bpj.2015.04.009
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author Zheng, Kaiyu
Rusakov, Dmitri A.
author_facet Zheng, Kaiyu
Rusakov, Dmitri A.
author_sort Zheng, Kaiyu
collection PubMed
description Sustained activation of NMDA receptors (NMDARs) plays an important role in controlling activity of neural circuits in the brain. However, whether this activation reflects the ambient level of excitatory neurotransmitter glutamate in brain tissue or whether it depends mainly on local synaptic discharges remains poorly understood. To shed light on the underlying biophysics here we developed and explored a detailed Monte Carlo model of a realistic three-dimensional neuropil fragment containing 54 excitatory synapses. To trace individual molecules and their individual receptor interactions on this scale, we have designed and implemented a dedicated computer cluster and the appropriate software environment. Our simulations have suggested that sparse synaptic discharges are 20–30 times more efficient than nonsynaptic (stationary, leaky) supply of glutamate in controlling sustained NMDAR occupancy in the brain. This mechanism could explain how the brain circuits provide substantial background activation of NMDARs while maintaining a negligible ambient glutamate level in the extracellular space. Thus the background NMDAR occupancy, rather than the background glutamate level, is likely to reflect the ongoing activity in local excitatory networks.
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spelling pubmed-44569982015-12-17 Efficient Integration of Synaptic Events by NMDA Receptors in Three-Dimensional Neuropil Zheng, Kaiyu Rusakov, Dmitri A. Biophys J Channels and Transporters Sustained activation of NMDA receptors (NMDARs) plays an important role in controlling activity of neural circuits in the brain. However, whether this activation reflects the ambient level of excitatory neurotransmitter glutamate in brain tissue or whether it depends mainly on local synaptic discharges remains poorly understood. To shed light on the underlying biophysics here we developed and explored a detailed Monte Carlo model of a realistic three-dimensional neuropil fragment containing 54 excitatory synapses. To trace individual molecules and their individual receptor interactions on this scale, we have designed and implemented a dedicated computer cluster and the appropriate software environment. Our simulations have suggested that sparse synaptic discharges are 20–30 times more efficient than nonsynaptic (stationary, leaky) supply of glutamate in controlling sustained NMDAR occupancy in the brain. This mechanism could explain how the brain circuits provide substantial background activation of NMDARs while maintaining a negligible ambient glutamate level in the extracellular space. Thus the background NMDAR occupancy, rather than the background glutamate level, is likely to reflect the ongoing activity in local excitatory networks. The Biophysical Society 2015-05-19 2015-05-19 /pmc/articles/PMC4456998/ /pubmed/25992724 http://dx.doi.org/10.1016/j.bpj.2015.04.009 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Channels and Transporters
Zheng, Kaiyu
Rusakov, Dmitri A.
Efficient Integration of Synaptic Events by NMDA Receptors in Three-Dimensional Neuropil
title Efficient Integration of Synaptic Events by NMDA Receptors in Three-Dimensional Neuropil
title_full Efficient Integration of Synaptic Events by NMDA Receptors in Three-Dimensional Neuropil
title_fullStr Efficient Integration of Synaptic Events by NMDA Receptors in Three-Dimensional Neuropil
title_full_unstemmed Efficient Integration of Synaptic Events by NMDA Receptors in Three-Dimensional Neuropil
title_short Efficient Integration of Synaptic Events by NMDA Receptors in Three-Dimensional Neuropil
title_sort efficient integration of synaptic events by nmda receptors in three-dimensional neuropil
topic Channels and Transporters
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456998/
https://www.ncbi.nlm.nih.gov/pubmed/25992724
http://dx.doi.org/10.1016/j.bpj.2015.04.009
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