Jim Beran's Abstract for TSC 2013, Agra, India

Below is Jim Beran's abstract for TSC 2013 as submitted on October 9, 2012. It includes links to related articles with further discussion and full citations.

Title:

Mere Protein Molecules? Or Mutating Machines?--How Evolution of Posttranslational Modifications (PTMs) Led to Microtubule-based Structures with Consciousness-specific Plasticity

Abstract:

In response to the hypothesis that microtubules play a part in consciousness, at least one skeptic has argued: "Microtubules are just protein molecules." [1]  But a typical microtubule includes thousands of tubulin protein molecules, and tubulin molecules of each type vary as a result of posttranslational modifications (PTMs) such as acetylation/deacetylation, phosphorylation, polyglutamylation, polyglycylation, tyrosination/detyrosination, etc. Further, groups of microtubules join to form various cytoskeletal structures, e.g. cross-linked by microtubule-associated proteins (MAPs), and participate in complex mechanical operations, e.g. during flagellar or ciliary movement, during mitosis, and, in neurons, during migration and during axon and dendrite growth. We therefore refer to microtubule-based cytoskeletal structures that participate in machine-like subsynapse operations as "cyto-machines". [2] This work explores hypothetical evolutionary paths that lead from simpler cyto-machines in pre-brain neurons to more complex dendritic cyto-machines with consciousness-specific features in brains like ours. Thanks to a suggestion from Dr. Travis Craddock that some PTMs approximate the time-scale at which conscious experience changes [3], we realized that processes that regulate PTM in cyto-machines (e.g. by regulating where, when, and how rapidly PTMs occur--generically "PTM regulation") might have initially evolved to increase stability of subsynapse cytoskeleton and later to change conscious experience. We therefore seek evolutionary paths that satisfy at least the following constraints:  (I)  Each of a path's transitions must be achievable by a set of DNA mutations that affects PTM regulation and that supports increased stability of subsynapse cytoskeleton; and (II)  there must be a plausible scenario (an "RTP scenario") in which one of the path's transitions leads to cyto-machines capable of changing conscious experience in response to synapse signals, i.e. an example of "real-time plasticity" or "RTP". We also propose several intuitive assumptions to help narrow the field of possible evolutionary paths:  (A)  An early evolutionary advance yielded PTM regulation that stabilizes subsynapse cytoskeleton in response to synapse signals; (B)  at least some of the path's transitions correspond to evolution of electromagnetic effects of the types we detect with EEG/MEG; and (C)  similarly, at least some transitions correspond to specialization of certain synapse signals to convey increased information of types provided by conscious experience, e.g. signals from a "grandmother synapse". And we propose a possible RTP scenario:  The evolutionary path led to multi-dendritic sets of electromagnetically coupling cyto-machines, each set responding to a respective highly informative synapse signal; the sets compete through interference, so that a shift occurs whenever one set takes over from another--we propose that a subsequent evolutionary transition enabled these shifts to change an organism's conscious experience, thus providing an example of RTP. Finally, we compare a number of evolutionary paths that satisfy these constraints and assumptions and that might have led to the proposed RTP scenario. If we can find further evidence for one such path, we will be more confident, not only that microtubules are more than just protein molecules, but also that dendritic cytoskeleton has features specific to consciousness. [1]  Private e-mail communication from Anirudh Kumar Satsangi, July 19, 2012. [2]  Compare, e.g., Wasteneys et al., ch. 14 in Nabi, Ed., Cellular Domains, 2011 re "Microtubules as Cellular Machines". [3] See also Hameroff et al., Journal of Integrative Neuroscience, 2010 and Craddock et al., PLOS Computational Biology, 2012 re microtubule phosphorylation and memory.