期刊
BIOPHYSICAL JOURNAL
卷 108, 期 10, 页码 2457-2464出版社
CELL PRESS
DOI: 10.1016/j.bpj.2015.04.009
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资金
- Wellcome Trust
- European Research Council
- Medical Research Council (UK)
- Biotechnology and Biological Sciences Research Council (UK)
- BBSRC [BB/J001473/1] Funding Source: UKRI
- MRC [G0600368] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/J001473/1] Funding Source: researchfish
- Medical Research Council [G0600368] Funding Source: researchfish
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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