Anatomy of Genius

Nobly reasonable? Infinitely facultative? Angelic and Godly?!
Wow! What a piece of work was Shakespeare!
But was he a genius? Was Bach, Da Vinci, or Einstein?
What do we mean by use of the word genius?

In this, the third of four posts, the intent is to bravely push on, away from the comfort and normalcy of home. Our journey began in a deep contextual fog, of historical, theistic, and social themes; tricky navigation to be sure! Now, with a stiff wind in our sails, we carry on to explore the isles of intelligent behavior – Cellular Biology and Micro Anatomy, and to reunite matter with genius.

A tall order! Or a tall tale?

Indistinct morphologies and a rebel arbiter
In opposition to the “prestigious authorities” of his time, Rudolf Ludwig Karl Virchow argued, during the mid-eighteen-hundreds, that the brain contains connective tissue. He described what he assumed to be connective tissue as, “a sort of putty [nervenkitt], in which the nervous elements are embedded”.1 The German term nervenkitt – coined and first used by Virchow, to identify the sticky mass he had observed enveloping neural cells – is translated into English as neuroglia; the word glia is derived from the Greek γλοία (“glue”). Shortly thereafter, in 1865, Otto Friedrich Karl Deiters reasoned that any cell that does not have an axon (“hauptaxencylinderfortsatz” – in English this word means something like main cylindrical extension) cannot be a nerve cell. Deiters’ hypothesis was confirmed in 1886 by Golgi’s superior staining technique.

Camillo_Golgi black_reaction

Camillo Golgi invented silver staining (“the black reaction”) in 1873, which enabled the visualization of nervous tissue with light microscopy.

Golgi called attention to the relationship between the endfeet of glial “protoplasmic prolongations” (known today as processes) with blood vessels. Nerve cells were very rarely observed to contact blood vessels, so glial cells were assumed to be the principal suppliers of nutrients, sugars and oxygen, to the “noble elements” (neurons) of the brain. Ernesto Lugaro first proposed that perivascular glial endfeet may serve as a detoxifying filter of substances that might enter from the blood into the brain, and that glial cells might remove toxic waste products of neuronal metabolism. And so it was that glia were assigned to the low caste of the cellular population of the central nervous system, and given the status of “support cells”, which is what the cannon of neurobiology has taught until very recently.

Current studies are showing that astroglia, or astrocytes (star-like cells), display a remarkable heterogeneity in morphology and function.2 Not all astrocytes exhibit a star-like morphology, not all express glial fibrillary acidic protein (GFAP – the compound currently used as a specific maker of astrocytes), and not all contact the vasculature. And apparently, it was never true that we use only one tenth of our brains – a conjecture based upon the assumption that the glia out number the neurons 10 to 1, and that only the “noble elements” do the thinking. A quantitative study performed by Bahney et al (2013), has concluded that “the ratio of glia to neurons in the human brain is approximately 1:1 rather than the 10:1 or 50:1 ratio previously assumed”.3 So, although astroglia comprise the most diverse cell type in the central nervous system, they are not, as Oberheim (2012) and many before her suggest, the most numerous.

In lieu of an unambiguous definition of this, most fascinating of cell types, and in an attempt to contextualize what may be a key anatomical aspect of genius, let us take a little swim in the relevant literature.

Dominium & Syncytium
Protoplasmic astrocytes stake-out, occupy, and maintain their own individual territories, thus creating micro-anatomical domains2 within the limits of the tentacle-like processes extended by each astrocyte cell body. Within an individual cell’s domain, the astrocyte membrane interacts with the membranes of several neurons, may envelop as many as two million synapses, as well as extending to a neighboring blood vessel, and to neighboring glia. Such interactions are mediated by the flattened endfeet of the elongated processes.4
neurovascular_unit
The entire complex (astrocyte, multiple neurons, other glia, and blood vessel) is known as a neurovascular unit.

Individual astroglial domains are integrated into a local superstructure called an astroglial syncytium, as a result of cytoplasmic sharing and of cytoplasmic streaming, mediated by gap junctions on endfeet. Astroglial syncytia are also anatomically segregated, each syncytium forming an anatomical computation structure. This is not to be confused with computational anatomynote 1 the term anatomical computation is used here to describe a multicellular network capable of physical computation. There is some resemblance, in meaning at least, to the macro scale anatomical computation described by Valero-Cuevas et al (2006), for the tendon network of the fingers5, and by Milo et al (2004), for various evolved and artificial networks6.
tendon_network_fingers
Schematic diagram of the tendon network of the fingers – an example of anatomical computation.

gap_junction
Schematic diagram of a gap junction and its subunits – the first slide (left side) shows a transmembrane protein (connexin), the second slide shows the (self)assembled connexin hexamer (hemichannel), the third slide shows three gap junctions formed by the (self)assembly of pairs of hemichannels.

astroglial_syncytium_gaps
Schematic diagram of an idealized 2-dimensional slice of an astroglial syncytium, showing gap junctions (green) at the ends of processes, cell nuclei (red).

astroglial_syncytium_paths
“Dancing Suns” – Schematic diagram of an idealized 2-dimensional slice of an astroglial syncytium, showing two (of very many) possible signalling pathways – a direct route (yellow), and the long way ’round (blue).

“Protoplasmic astrocytes of the cortex are highly coupled cells. After a single cell injection of biocytin, a gap junction-permeable dye, an average of 94 cells spanning a radius of approximately 400 μm can be visualized and hence appear networked through gap junctions”.2 Glia are known to receive and transmit molecular gliotransmitters, propagated, possibly bidirectionally, via the cellular processes. Furthermore, processes are capable of propagating ionic waves and are known to conduct action potentials (the principal form of neuronal signal transduction), and thus are capable, in principle, of conducting high-speed electronic communications.7 It is conceivable that a somatic pulse, generated by the rhythmic cardiac function, is made use of by glial syncytia in order to drive cytoplasmic compounds, selectively and/or diffusively, through a brain-wide-web (neuro-glial syncytium).
syncytium_capillaries
Astrocytes (red), blood vessels (green), and ganglion cell nuclei (blue).8

The conscious pilot
“Glial cells […] have gap junction connections with neurons and other glia, extend great distances throughout the brain, and could enable brain-wide gap junction networks. […] Neurons connected by gap junctions have continuous internal cytoplasm and synchronized membranes and behave like one giant neuron. Membrane potentials on one side of a dendritic–dendritic gap junction induce a spikelet or prepotential into the opposite side, integrating dendritic potentials (along with axonal inputs) to drive synchrony. […] Neurons and glia connected by gap junctions may be viewed as subsets of Golgi’s threaded-together reticulum, described as syncytia […]. Placement, openings, and closings of gap junctions are regulated by intra-neuronal calcium ions, cytoskeletal microtubules, and/or phosphorylation via G-protein metabotropic receptor activity. As various gap junctions open and close, form and disappear, the topology, location, and extent of synchronized dendritic web syncytia can change and move sideways through input/integration layers of axonal–dendritic networks throughout the brain. [The] billions of brain neurons and glia provide a near-infinite variety of topological syncytia, representational Turing structures which may be isomorphic with cognitive or conscious content. Fleetingly shifting […] spatiotemporal envelopes of dendritic synchrony [may] correlate with conscious scenes and frames. […] Any fine-scale [i.e. subcellular] process mediating consciousness occurring on membrane surfaces or within neuronal interiors could be structurally unified and temporally synchronized by gap junctions and dendritic webs”.9
fine_scale_Hamerhoff
Schematic diagram of two neural dendrites, or glial processes (or one of each), connected by a gap junction. Within each cytoplasmic interior, microtubules (spotted bars) are connected by microtubule-associated proteins (lines interconnecting the spotted bars). Curved lines and interference patterns represent possible fine-scale processes underlying consciousness (e.g., electromagnetic fields, calcium ion gradients, molecular reaction–diffusion patterns, actin sol-gel dynamics, glycolysis, classical microtubule information processing, and/or microtubule quantum computation with entanglement and quantum coherence). These processes can extend through gap junctions and in principle throughout brain-wide webs. Thus, cellular integration webs may unify (on a brain-wide basis) fine-scale processes comprising consciousness.9

In addition to gap junction coupling, Oberheim et al (2012), propose that hemichannel (half a gap junction) formation allows for regulated release or uptake of gliotransmitters to and from the extracellular matrix.

Tripartite Synaps
“Astroglia can affect neuronal excitability, possibly modulate synaptic transmission and synchronise synaptic events. It should be stated, however, that the role and relevance of gliotransmission for information processing in the brain remains controversial”.10

Synapses comprise three parts; a presynaptic terminal, the postsynaptic neuronal membrane, and an eveloping astrocyte. Neurotransmitters that are released from the presynaptic terminal activate receptors that are embedded in the membranes of the postsynaptic neuron and the local astrocyte, thus potentiating the postsynaptic neuron and creating a Calcium ion (Ca2+) signal in the astrocyte. The latter can propagate through the astroglial cell body and through the astrocytic syncytium, thus allowing for triggering of neurotransmitter release from the astrocyte, which in turn may signal the pre- and postsynaptic neurons.10

The generation and maintenance of trophic molecules, signalling molecules, various second messengers, metabolic substrates, and other stuff that comprises inter- and intracellular, and inter- and intrasyncytial signal waves, is complex, involving selective diffusion through gap junctions, and endo- and exocytosis via vesicles, to and from astrocytes, neurons and the extracellular matrix. Importantly, astroglial signalling is on a much slower time scale than is neuronal signalling. The former ranging in the seconds or minutes, the latter ranging in the milliseconds.

Far from playing the lowly role of support cells, astrocytes, and the syncytia in particular, should probably be considered integrators, modulators, and interpreters of molecular signalling cascades. My intuition is that the glia do the messy and difficult part of thinking, and that they create, regulate and keep the rapid, rational, machine-like, neural networks. That in a sense it is the neural networks which play the supporting role, much as we humans do the messy work of real intelligent thinking, and have created, regulate and keep the rapid, rational, networks of machine systems in order to aid our endeavors.

– a messy little aside –
The interconnected brain, a system of syncytia, surely forms a meta-syncytium. This concept seems a much better fit with Aristotelian animism, than with Descartesian substance dualism and “nonphysical substance”(?!) – an abhorrent conception if ever I encountered one! No, the mind (spirit, soul, consciousness, sapience, genius…) is a somatic function. It is time for us to bravely correct Descartes’ erroneous vision.

We think because we are.
– or in native Descartesian J’existe, donc je pense.

Anatomy of animism
The following section presents an argument for Aristotelian (pagan) animism, by exposure of two experimental concepts:
a) intelligent behaviors of slime molds.
b) intelligent behaviors of plant roots.

a) Physarum polycephalum develops as a multinucleate syncytium, and has been reported to display behaviors indicative of intelligence, such as learning, memory formation and anticipation. In an experimental study reminiscent of Skinner’s operant conditioning (described in an earlier post, titled “The Worldly and The Amish“), Saigusa et al (2008), exposed the plasmodium of P. polycephalum to periodic changes of humidity and temperature, thus producing a temporary adverse environmental state at regular intervals. As is the case with all life forms, P. polycephalum responds to adverse environmental change, in this case by slowing its growth and territorial exploration, here termed “spontaneous in-phase slowdown” (SPS). After a set of three regularly timed exposures to the adverse condition, the organism is reported to have anticipated a fourth and fifth exposure, in both cases observed as a significant SPS. However, the fourth and fifth SPSs were not induced by the experimenters (i.e. there was no adverse environmental condition). Thus, the authors “conclude that the Physarum plasmodium can perform a primitive version of brain function (that is, memory and anticipation)”.11

C. Reid et al (2012), have commented that “when solving a maze or connecting several food sources using the most efficient network, the slime mold first explores its entire environment, with cytoplasm simultaneously covering all exploration space, before retracting cytoplasm from areas that do not contain food. The result is the construction of a single tubule when connecting two food sources only, or an efficient tubule network between food-source nodes”.11

This proliferative exploration prior to the retraction of non-reinforced connections, bears great similarity to synaptic pruning discussed in an earlier post, titled “Meta-matricity“.
Tetsu_Saigusa
Tetsu Saigusa holding two petri dishes containing Physarum polycephalum. In the dish on the right the slime mold has covered the entire exploration space available to it. In the dish on the left, after self-pruning a single cytoplasmic tubule connects two nutrient sources.

During exploratory foraging the plasmodium leaves behind a mat of nonliving, extracellular polymeric substance (EPS). Reid et al suggest that the organism’s tendency to avoid the EPS in future foraging, indicates the use of EPS, by P. polycephalum as an externalized spacial memory. The authors also deem the avoidance behavior to be a choice, because if no previously unexplored territory is available, the avoidance stops. I assume that having exhausted all options for the acquisition of food, the starving organism is forced to eat the EPS which it had previously secreted. Whether the behavior observed in association with the situation, as described by Reid et al constitutes “choice”, is, I think, debatable. But then in all fairness, choice, or preference, or indeed free will, are all rather poorly understood.
Pp_externalized_memory
Photograph of P. polycephalum plasmodium showing (A) extending pseudopod, (B) search front, (C) tubule network, and (D) extracellular slime deposited where the cell has previously explored. The food disk containing the inoculation of plasmodial culture is depicted at (E).12

b) Concurrent with these findings, advances in molecular and cell biology, and ecology, have begun to identify plants as sensing, communicative and cooperative, problem solving organisms. However, it was Charles Darwin, in collaboration with his son Francis, who first proposed that plants behave intelligently. Darwin had spent the last twenty years of his life studying plant roots, and described them as behaving like the lower animals, principally the invertebrate soft bodied animals, such as worms and slugs. With the root apex seated at the anterior pole (front end) of the plant body where it acts as a “brain-like organ”. Darwin’s root-brain hypothesis13 has been forgotten, or ignored, for well over one hundred years, but recent experimental findings have collectively created a conceptual scaffold in support of Darwin’s root-brain. In particular the higher plants, can no longer be placed outside the realm of cognitive, animated, animal living systems – a dichotomy traceable to Aristotle – possibly as a result of failing to appreciate the varying time-scales of living organisms; plant movements, due to their greatly reduced velocity, are not as readily observable as are animal movements.
Mycorrhizae
Plant roots, shown here as part of a mycorrhizal, mutualistic symbiotic relationship.

“The common descent of all organisms is the central pillar of Charles Darwin’s theory of evolution and […] the unity of life implied thereby is a revelation of both beauty and simplicity. By the same token, the existence of a plant neurobiology harmonises with the neurobiology of animals. […] In keeping with Charles Darwin’s theory of common descent of all organisms, a unification of animals/humans and plants according to their body polarity is possible and thereby removes from view the Aristotelian dichotomy between plant and animal organisms. [Plants] possess a sensory-based cognition which leads to behavior, decisions and even displays of prototypic intelligence”.14

Bibliography and Notes
note 1. In contrast to anatomical computation (aka: somatic computation), computational anatomy is defined as a field of neuroanatomy utilizing various imaging and computational techniques to model and quantify the spatiotemporal dynamics of neuroanatomical structures.

1) G. Somjen, “Nervenkitt: Notes on the History of the Concept of Neuroglia”, (1988), GLIA, Vol. 1, p. 2-9, PDF available, https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&ved=0CCYQFjAB&url=https%3A%2F%2Fwiki.brown.edu%2Fconfluence%2Fdownload%2Fattachments%2F74847169%2FNervenkitt%2BNotes%2Bon%2Bthe%2BHistory%2Bof%2Bthe%2BConcept%2Bof%2BNeuroglia.pdf&ei=HZTHVN67J4OuPInrgJAL&usg=AFQjCNH8k7st6lX1MiuLhZ2TJB9SBwBKEQ&bvm=bv.84607526,d.ZWU

2) N. Oberheim et al, “Heterogeneity of Astrocytic Form and Function”, (2012), Vol. 814, p. 23-45, Methods in Molecular Biology, https://www.researchgate.net/publication/51855335_Heterogeneity_of_Astrocytic_Form_and_Function

3) J. Bahney et al,”Validation of the isotropic fractionator: Comparison with unbiased stereology and DNA extraction for quantification of glial cells”, (2013), Journal of Neuroscience Methods, Vol. 222, p. 165–174, http://www.sciencedirect.com/science/article/pii/S0165027013003786

4) M. Merlini et al, “In vivo imaging of the neurovascular unit in CNS disease”, vol. 1(2), p. 87-94, IntraVital, http://www.tandfonline.com/doi/full/10.4161/intv.22214#.VMooxMbYdFU

5) Valero-Cuevas et al, “The tendon network of the fingers performs anatomical computation at a macroscopic scale”, (2006), TRANSACTIONS ON BIOMEDICAL ENGINEERING, http://bme.usc.edu/assets/005/55499.pdf

6) Milo et al, “Superfamilies of Evolved and Designed Networks”, (2004), Science, http://www.sciencemag.org/content/303/5663/1538.abstract

7) T. Otis & M. Sofroniew, “Glia get excited”, (2008), Nature Neuroscience Vol. 11, p. 379 – 380, http://www.nature.com/neuro/journal/v11/n4/full/nn0408-379.html

8) Fernández-Sánchez and Cuenca, (2010), Vision Research Picture Competition, http://www.vision-research.eu/index.php?id=581

9) S. Hamerhoff, “The conscious pilot – dendritic synchrony moves through the brain to mediate consciousness”, (2009), Journal of Biological Physics, http://www.pubfacts.com/fulltext/19669425/The

10) Adapted from: H. Kettenmann, A. Verkhratsky, “Neuroglia – Living Nerve Glue”, (2011), Fortschritte der Neurologie und Psychiatrie, vol. 79, p. 588-597, http://www.networkglia.eu/en/astrocytes (sponsored by the journal Glia, http://onlinelibrary.wiley.com/doi/10.1002/glia.v63.2/issuetoc)

11) T. Saigusa et al, “Amoebae Anticipate Periodic Events”, (2008), Physical Review Letters, 100(1): 018101, http://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/33004/1/PhysRevLett_100_018101.pdf

12) C. Reid et al, “Slime mold uses an externalized spatial “memory” to navigate in complex environments”, (2012), vol. 109(43), p. 17490–17494, Proceedings of the National Academy of Sciences, http://www.pnas.org/content/109/43/17490.full

13) U. Kutschera & K. Niklas, Darwin’s root-brain hypothesis (p. 1343), in “Evolutionary plant physiology: Charles Darwin’s forgotten synthesis”, (2009), Springer-Verlag, http://www.evolutionsbiologen.de/media/files/pdfs/darwin/2009KutNiklas.pdf

14) F. Baluškaet al, “The ‘root-brain’ hypothesis of Charles and Francis Darwin: Revival after more than 125 years”, (2009), Plant Signaling & Behavior, Vol. 4, p 1121-1127, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819436/

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