Related Experiment Video
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Real-time Electrophysiology: Using Closed-loop Protocols to Probe Neuronal Dynamics and Beyond
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Ion dynamics at the energy-deprived tripartite synapse
Manu Kalia1, Hil G E Meijer1, Stephan A van Gils1
1Applied Analysis, Department of Applied Mathematics, University of Twente, Enschede, The Netherlands.
Plos Computational Biology
|June 18, 2021
Summary
Energy deprivation causes synaptic failure and brain damage, particularly in aging individuals. A biophysical model reveals that reduced extracellular space promotes this transition to a pathological state, offering insights into stroke vulnerability.
Area of Science:
- Neuroscience
- Computational Biology
- Biophysics
Background:
- Tripartite synapses, crucial for neurotransmission, rely on ATP. Energy deprivation leads to synaptic failure, ion gradient breakdown, and cell damage, contributing to ischemic stroke consequences.
- Differential vulnerability to ischemic stroke based on age and brain region is not well understood.
Purpose of the Study:
- To develop a biophysical model of glutamatergic synapses to identify key factors in synaptic failure during energy deprivation.
- To investigate the role of ion dynamics and extracellular space in stroke vulnerability.
Main Methods:
- Developed a comprehensive biophysical model of a glutamatergic synapse.
- Incorporated dynamics of key ions (Na+, K+, Ca2+, Cl-) and glutamate.
- Calibrated the model with experimental data.
Main Results:
- Confirmed the critical role of the Na+/K+-ATPase in maintaining cellular homeostasis.
- Demonstrated the existence of two stable states: physiological and pathological.
- Showed that reduced extracellular space fraction, as seen in aging, favors the transition to the pathological state.
Conclusions:
- Energy deprivation can force synapses into a pathological state, potentially reversible by blocking specific ion channels.
- Reduced extracellular space increases susceptibility to ischemic damage, offering a mechanism for age-related vulnerability.
- The model provides insights into brain recovery from energy deprivation with relevance for stroke diagnosis and treatment.
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