Short-term synaptic plasticity modulates the outcome of neurodegenerative diseases
- 1CityU Shenzhen Research Institute, Shenzhen, Guangdong, China
- 2Department of Neuroscience, College of Biomedicine, City University of Hong Kong, Kowloon, Hong Kong SAR, China
Abstract
IntroductionAlzheimer's disease (AD) is characterized by progressive neuronal loss and synaptic dysfunction that disrupt memory-encoding neural circuits. Short-term synaptic plasticity (STP), which governs transient activity-dependent changes in synaptic efficacy on millisecond-to-second timescales, is a potentially targetable mechanism for dynamically compensating circuit-level deficits without requiring structural repair. This study asked whether re-tuning short-term facilitation and depression in surviving synapses can restore engram recall and network oscillations in a computational model of AD.MethodsUsing the NEST Simulator, a spiking neural network of 1,000 Hodgkin-Huxley excitatory neurons and 250 leaky integrate-and-fire inhibitory neurons was constructed with embedded memory engram assemblies. AD pathology was modeled through accelerated neuronal loss and pathological hyperexcitability. Synaptic dynamics were governed by the Tsodyks-Markram model. Compensatory interventions were evaluated by systematically sweeping the facilitation time constant τfac and the recovery time constant τrec across a two-dimensional parameter space. Engram recall fidelity was quantified by the selectivity ratio Γ, and network-level oscillatory dynamics were assessed from the power spectral density of the simulated local field potential (LFP).ResultsIncreasing τfac from 500 ms to 1,250ms rescued engram selectivity in the AD model at intermediate synaptic-weight regimes that were inaccessible at baseline, and partially restored theta-band LFP power while fully restoring alpha-band LFP power. The τrec sweep revealed a trade-off: increasing τrec reduced Γ, whereas decreasing it maximized recall, with only small accompanying changes in background excitability.DiscussionShort-term synaptic facilitation (STF) and short-term synaptic depression (STD) modulation exert mechanistically distinct compensatory effects. The sweeps identify bounded parameter windows within which dynamic re-tuning of surviving synaptic circuits can mitigate AD-related deficits in engram selectivity and oscillatory power without structural repair.
Related
- Synaptic transmission and plasticity: molecular mechanisms, biological functions and therapeutic opportunities in neurodegenerative diseases.
- HMGB1 functional plasticity in neurodegenerative diseases and its translational implications
- Genetic and Molecular Mechanisms of Synaptic Plasticity in Perioperative Delirium: From Neuroinflammation to Circuit Dysfunction and Recovery
- Can Music-Induced Brain Plasticity Delay Neurodegenerative Disorders in Musicians? Review and Cases
- Myelin Maintenance and Addition Regulate Synaptic Plasticity in the Adult Mouse Cortex
BibTeX
@article{zhang2026shortterm,
title = {{Short-term synaptic plasticity modulates the outcome of neurodegenerative diseases}},
author = {Han Zhang and Han Zhang and Yusuf Mohideen and Chi Chung Alan Fung and Chi Chung Alan Fung},
journal = {Frontiers in Computational Neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fncom.2026.1923602},
url = {https://doi.org/10.3389/fncom.2026.1923602},
note = {CC BY},
}
RIS
TY - JOUR
TI - Short-term synaptic plasticity modulates the outcome of neurodegenerative diseases
AU - Han Zhang
AU - Han Zhang
AU - Yusuf Mohideen
AU - Chi Chung Alan Fung
AU - Chi Chung Alan Fung
PY - 2026
DA - 2026/10/23
JO - Frontiers in Computational Neuroscience
DO - 10.3389/fncom.2026.1923602
UR - https://doi.org/10.3389/fncom.2026.1923602
AB - IntroductionAlzheimer's disease (AD) is characterized by progressive neuronal loss and synaptic dysfunction that disrupt memory-encoding neural circuits. Short-term synaptic plasticity (STP), which governs transient activity-dependent changes in synaptic efficacy on millisecond-to-second timescales, is a potentially targetable mechanism for dynamically compensating circuit-level deficits without requiring structural repair. This study asked whether re-tuning short-term facilitation and depression in surviving synapses can restore engram recall and network oscillations in a computational model of AD.MethodsUsing the NEST Simulator, a spiking neural network of 1,000 Hodgkin-Huxley excitatory neurons and 250 leaky integrate-and-fire inhibitory neurons was constructed with embedded memory engram assemblies. AD pathology was modeled through accelerated neuronal loss and pathological hyperexcitability. Synaptic dynamics were governed by the Tsodyks-Markram model. Compensatory interventions were evaluated by systematically sweeping the facilitation time constant τfac and the recovery time constant τrec across a two-dimensional parameter space. Engram recall fidelity was quantified by the selectivity ratio Γ, and network-level oscillatory dynamics were assessed from the power spectral density of the simulated local field potential (LFP).ResultsIncreasing τfac from 500 ms to 1,250ms rescued engram selectivity in the AD model at intermediate synaptic-weight regimes that were inaccessible at baseline, and partially restored theta-band LFP power while fully restoring alpha-band LFP power. The τrec sweep revealed a trade-off: increasing τrec reduced Γ, whereas decreasing it maximized recall, with only small accompanying changes in background excitability.DiscussionShort-term synaptic facilitation (STF) and short-term synaptic depression (STD) modulation exert mechanistically distinct compensatory effects. The sweeps identify bounded parameter windows within which dynamic re-tuning of surviving synaptic circuits can mitigate AD-related deficits in engram selectivity and oscillatory power without structural repair.
SN - 1662-5188
ER -