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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Biophysical Society
2015
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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. |
format | Online Article Text |
id | pubmed-4456998 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Biophysical Society |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT zhengkaiyu efficientintegrationofsynapticeventsbynmdareceptorsinthreedimensionalneuropil AT rusakovdmitria efficientintegrationofsynapticeventsbynmdareceptorsinthreedimensionalneuropil |