Bioenergetic coherence as a determinant of neuronal function: an in silico validation

This report presents a systems-level, in silico validation framework demonstrating that neuronal information processing, plasticity, and survival are causally constrained by bioenergetic coherence. Using publicly documented parameters for calcium dynamics, CaMKII activation, and mitochondrial ATP/NADH production, simulations show that identical electrical stimulation patterns yield fundamentally different outcomes depending on energy availability. The framework highlights that neuronal vulnerability is state-dependent, with energetic imbalance preceding excitotoxic collapse and propagating across networks. Observations are fully reproducible, non-proprietary, and provide a mechanistic basis for understanding neurodegeneration from an energy-centric systems perspective.

Keywords:
Neuronal bioenergetics, Ca²⁺ dynamics, CaMKII, ATP/NADH, in silico validation, energetic coherence, neurodegeneration, network dynamics

Bioenergetic Coherence as a Determinant of Neuronal Function

Bioenergetic Coherence as a Determinant of Neuronal Function is a scientific perspective and in silico validation report authored by Carlos J. Pérez Pulido at the ISHEA Institute. The work investigates how neuronal information processing, plasticity, and survival depend on the energetic state of the system, rather than on electrical stimulation patterns alone.

Using computational simulations of calcium dynamics (Ca²⁺), CaMKII activation, and mitochondrial ATP/NADH availability, the study demonstrates that identical electrical inputs can produce either normal neuronal function or excitotoxic collapse depending on bioenergetic efficiency. The framework models neurons as dynamic systems where energy supply constrains information processing, plasticity, and network stability.

Key findings include:

Neuronal function is state-dependent, not stimulus-dependent.

Energetic imbalance precedes molecular or electrophysiological failure.

Dysfunction can propagate through neuronal networks even without overt pathology.

Ca²⁺ dynamics act as primary informational mediators, while ATP and NADH act as enabling constraints.

The report emphasizes reproducibility and transparency, using publicly available parameters and open-source computational methods. It offers a systems-level interpretation of neurodegeneration, suggesting that energetic coherence is a critical organizing principle for neuronal health and network resilience.