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Wang DW, et al

Heterosynaptic plasticity is a calcium-dependent phenomena, whether the source of [Ca 2+ ] i rise is strong local activation and local spread to inactive synapses or more global influx through voltage gated channels activated by back-propogating action potentials and amplified by release from internal stores

This mitochondrial failure is the direct biochemical driver of the profound, debilitating fatigue and post-exertional malaise (PEM) that patients experience after even minor physical or cognitive exertion