Computational modeling framework demonstrates role-separated memory reconstruction across neural and astrocytic states, highlighting rigorous verification requirements for multicellular engrams.
From Tripartite Synapses to Multicellular Engrams develops a role-separated account of how neuronal ensembles, astrocytic state, neuromodulation, metabolism, and extracellular conditions may jointly contribute to memory reconstruction. It distinguishes content from indexing, access, eligibility, stabilization, precision, and general state, then specifies the perturbation, rescue, bypass, transport, and uncertainty tests needed to separate those alternatives. The paper includes four executable synthetic research programs. Together they show that a model can succeed under one measurement regime and fail or reverse under another; that high coverage can conceal nearly complete ambiguity; and that repairing a confounded tool-by-promoter allocation does not guarantee adequate power or biological identification. All favorable, adverse, null, unresolved, and implementation results remain preserved. A bounded Lean certificate verifies finite allocation, count, access, fitted-capacity, evidence-history, interpretation, and endpoint-seal invariants. The formal result does not prove a biological astrocyte memory role, validate Self-Aware Networks, or establish clinical efficacy or safety. The future biological endpoint remains sealed.
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Micah Blumberg (2026) studied this question.
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