s A Derived Mechanism of Nervous System Functions Explains Aging-Related Neurodegeneration as a Gradual Loss of an Evolutionary Adaptation

Background: Solving the nervous system requires understanding how it generates inner sensations of "mind" within it. It was possible to derive a hypothesis of brain functions where the formation of a spectrum inter-postsynaptic (inter-spine) functional LINKs (IPLs) are the key structural changes responsible for encoding at the time of learning and are used for inducing the inner sensation of memory, both taking place at millisecond timescales. Since stages of ontogeny reflect possible stages of evolution, it is possible to examine whether IPLs have features of an evolved mechanism. Objective: To examine whether 1) IPLs have features of an evolved mechanism, 2) significant neuronal death during ontogeny leads to evolutionary adaptations for preventing cell death among the surviving neurons, and 3) loss of these adaptations lead to cellular changes that can cause agingrelated neurodegeneration. Methods: Key milestone changes of the ontogeny of the nervous system were examined to test whether they match with a feasible sequence of steps that lead to the formation of IPLs. Results: Several developmental stages can explain a probable sequence of events that lead to IPL formation among synaptically-connected neurons. When internal sensations generated by the IPLs started providing survival advantage, evolution has started preserving the IPL circuitry. A stage of inter-spine fusion possibly leads to a) significant neuronal death during the early stages of development, and b) trigger an adaptation in the surviving cells to stabilize and prevent the IPLs from undergoing fusion. Since there are no irreversible steps for maintaining the stability of IPLs, agingrelated factors may destroy the adaptation mechanism and destabilize the IPLs predisposing them to cause neurodegeneration. Conclusion: The derived testable IPL mechanism that can explain nervous system functions is capable to have evolved. An adaptation to prevent IPL hemifusion from progressing to fusion is likely the last stage of nervous system evolution. Since the IPL mechanism is utilized during every event of learning, any aging-related factors that can weaken this adaptation can cause IPL fusion and lead to neurodegeneration.