{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "CityU Shenzhen Research Institute, Shenzhen, Guangdong, China",
    "Department of Neuroscience, College of Biomedicine, City University of Hong Kong, Kowloon, Hong Kong SAR, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Han Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Han Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Yusuf Mohideen"
    },
    {
      "affs": [
        1
      ],
      "name": "Chi Chung Alan Fung"
    },
    {
      "affs": [
        0
      ],
      "name": "Chi Chung Alan Fung"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7q3x8t86a9gmy.bib",
  "cited_by": 0,
  "doi": "10.3389/fncom.2026.1923602",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fncom.2026.1923602/full",
  "id": "7q3x8t86a9gmy",
  "issns": [
    "1662-5188"
  ],
  "landing_url": "https://doi.org/10.3389/fncom.2026.1923602",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC321-571"
    ],
    [
      "openalex",
      "2804|Neuroscience and Neuropharmacology Research"
    ]
  ],
  "openalex": "W7223368678",
  "pdf_url": "https://www.frontiersin.org/journals/computational-neuroscience/articles/10.3389/fncom.2026.1923602/pdf",
  "pmcid": "PMC13739712",
  "pmid": "42996676",
  "published": "2026-10-23",
  "publisher": "Frontiers Media S.A.",
  "ris": "https://research.draconitic.com/paper/7q3x8t86a9gmy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:48Z",
      "native_id": "bf42e317191b4a1baa380e4b4541e007",
      "source": "doaj",
      "url": "https://doi.org/10.3389/fncom.2026.1923602"
    },
    {
      "first_seen": "2026-11-09T15:20:41Z",
      "native_id": "MED:42996676",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42996676"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Neuroscience and Neuropharmacology Research",
      "subfield": "neuroscience"
    }
  ],
  "title": "Short-term synaptic plasticity modulates the outcome of neurodegenerative diseases",
  "title_text": "Short-term synaptic plasticity modulates the outcome of neurodegenerative diseases",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T15:20:41Z",
  "url": "https://research.draconitic.com/paper/7q3x8t86a9gmy",
  "venue": "Frontiers in Computational Neuroscience",
  "versions": []
}