måndag 21 mars 2011

Neural communication outside synapses III. Biocentric wiev, homeostasy and consciousness.

The physical world is not composed of material particles, but of objective tendencies or potentialities, and they compactify, become "discrete" and actual events (criticality), but it needs the intervention of a conscious (free and subjective) agent. The objective tendencies and potentialities are only the half of the equation; for a full explanation and understanding of the universe you need the other half. This is where Einstein left us with the quantum gravity, and Schrödinger with his cat-analogy. Maybe they were almost there, but needed a huge jump in our consciousness - to abandon the biocentric and reductionistic worldwiev. We, our bodies, are not the big centers of Selves?

We have two selves, one small = our bodys sensations and reactions, and one big = our magnetic body, that is an onionlike structure in TGD.

There is no Anthropic principle? The concept of a 'conscious' act is wrongly understood. Consciousness is a 'value', something we get out of a measurement, or symmetry breaking, transformation, perception etc. - always linked to time. It is of course there also before (its precursors), but 'out of reach', spread out, diffuse and coherent, entangled. When we measure it we sample it and make it 'discrete' - for us. But it continues to be diffuse out there mostly. A small part of it is 'collapsed' into decoherence (a representation) and tied again to a new pattern, a new coherence, in an oscillating pattern. We create a mirror image of universe inside our body and brain. We internalize our own subjective Universe.

What is 'it'? Look at the double slit experiment. It is the 'nothing' in creation. Is it information? Quantum world? Vacuum? Primes or algebraic functions, non-determinism?

It is the cause. And it is 'nothing', something massless.

If we look at the control function of life, it is usually a very small signal, maybe even massless light, magnetism, electrochemical gradients etc. Coherent light sources have been widely used in control schemes that exploit quantum interference effects to direct the outcome of photochemical processes. Biophotons a la Popp, mediator between body and soul, DNA-waves that creates 'memories' as seen by Gariaev, Pitkänen and Montagnier...

The smaller signal, the better? But also its stability is important. The geomagnetic signal is most stable, as Becker said? Becker's research was about regeneration, and DC-fields were important, also induced ones. Should we then differentiate these DC-signals as endogen and exogen?

So the important side is not in the ordinary matter. Einstein saw the interference. The expansion and compression of strings/waves/particles. Time as an important factor.

Henry Stapp in"Mindful Universe" "Heisenberg’s ontology is about sudden events and about ‘objective tendencies’ for such events to happen. The natural ontological character of the ‘physical’ aspect of quantum theory, namely the part described in terms of a wave function or quantum state, is that of a ‘potentia’ or ‘tendency’ for an event to happen. Tendencies for events to happen are not substance-like: they are not static or persisting in time. When a detection event (measurement) happens in one region, the objective tendency for such an event to occur elsewhere changes abruptly. Such behavior does not conform to the philosophical conception of a substance. Thus, neither the event nor its tendency to happen are ontologically substantive or self-sufficient: they are intrinsically connected to one another. Descartes’ identification of two different ‘substances’ in reality is neither helpful for nor concordant with quantum theory. However, the conception of two differently described aspects of reality accords with both the theoretical and the practical elements of quantum theory." (pp. 103-104)

Copenhaguen interpretation of quantum mechanics is essentially dualistic and, therefore, incompatible with a purely mechanistic-materialistic worldview. In his words: "...according to the new conception, the physically described world is built not out of bits of matter, as matter was understood in the nineteenth century, but out of objective tendencies – potentialities – for certain discrete, whole actual events to occur. Each such event has both a psychologically described aspect, which is essentially an increment in knowledge, and also a physically described aspect, which is an action that abruptly changes the mathematically described set of potentialities to one that is concordant with the increase in knowledge. "

The synaptic Self.
Joseph LeDoux, 2002, talked of synapses as analog to a self in Synaptic Self: How Our Brains Become Who We Are. The self is sustained by coordinated learning which occurs simultaneously in diverse systems (plasticity), which many function implicitly or unconsciously. "Synapses also allow interactions between mental processes, allowing us to remember the important stuff in life better than the trivial. What's more, synapses encode the essence of the individual, allowing us to be the same person from moment to moment, week to week and year to year. In short, the self is synaptic. " "A key feature of the brain is its remarkable ability to form associations between coincident events, allowing organisms to learn from the past and thereby predict the future. When individual neurons are coincidently active they will promote a strengthening of synaptic connections. Hebbian associative plasticity. Coincidence detection likely also occurs between neurons within micro circuits, in the brain of a behaving organism variable latencies of coincident external signals will result because of different sensory signals via separate afferent paths, as well as separate regional processing of sensory signals. To accommodate the variable latencies and still make associations between the externally coincident events, the brain uses such tools as oscillations and neuronal ensemble activity within microcircuits, both of which can facilitate coincidence detection ." Memory formation not only involves synaptic strengthening in feedforward circuits, it also involves reverberating signals in ensembles of neurons - is this the same as reentrant loops a la Edelman (for stability, predictibility?)? Amygdala is seen as an amplifying or bracing relaystation, simply a modulator invoked in behavioral response and learning, emotional memory formation? This is essentially the same function as acupuncture points throughout the body. So brain 'organs' may function as acupoints?

As correlated activity of presynaptic and postsynaptic neurons drives strengthening of specific synapses, the postsynaptic neuron will be driven more strongly, and so presynaptic inputs that were initially only poorly correlated with postsynaptic firing will be better able to trigger firing of the postsynaptic neuron, and they too can become strengthened even without a triggering environmental stimulus.

A reentrant loop is a structural motif that goes only halfway through the membrane and then turns back to the side from which it originates. The question of what causes the reentrant loops to form such a unique topology is still unanswered. Reentrant loops have very low hydrophobicity around the deepest point buried in the membrane and relative high hydrophobicity close to the membrane surfaces. We speculate that this hydrophobicity distribution is a major force that stabilizes the unique reentrant loop structure. Our results also show that this hydrophobicity distribution results in special patterns on protein sequences, which can be captured using profile hidden Markov models (HMMs). The resulting profile HMMs can detect reentrant loops on protein sequences with high sensitivity and perfect specificity. - linked to CpG islands, serotonin, DNA, epigenetics, telomers and cancer?

This is mainly not seen as enough today. Self is NOT only synaptic?
Consciousness being a byproduct of neural activity, with activity seen in higher brainwaves, is not true either. This is the signal, and signal is not the same as consciousness.

Conciousness cannot exist as synapes to synapes electrical communication (synaptic Self), conciousness is expressed in a complex electromagentic field, as feed-back loops, feed forward loops, reentrant loops in the membrane or parts of brains involving many, many neurons, etc. Field effects are most important in the microcolumns. I don't think such a study is possible (time-resolution inefficient?), but this is a complex system effect, therefore the scientific method is not adequate, this is not achieved in any single neuron. As electrical transfer is biniary by nature, it is further evidenced that groups of neurons dont reach singularity (measurement status for consciousness?) via electrical transfer (consider the limited connections). Therefore the bulk of compuation must be based in electromagetic field. We should have tools to measure also quantum properties directly.

Conscious awareness cannot be tied to a special region of the brain.
It's called an illusion because it's not what we think it is. For example, conscious decisions aren't causally efficacious: Conscious awareness of a decision follows actions that logically should follow the decision. That tells us that consciousness is some sort of instant replay function. As a relaxation to ground state?

Homeostatic synaptic scaling.
'The Self-Tuning Neuron: Synaptic Scaling of Excitatory Synapses' by Turrigiano 2008, she writes about "Homeostatic synaptic scaling, that is a form of synaptic plasticity that adjusts the strength of all of a neuron’s excitatory synapses up or down to stabilize firing." Neurons detect changes in their own firing rates through a set of calcium-dependent sensors that then regulate receptor trafficking to increase or decrease the accumulation of glutamate receptors at synaptic sites.

This sounds familiar, doesn't it? Homeostasis is a total stress reaction, that tries to keep a balance, sometimes via amplification (allostasis). But she forget to mention extrasynaptic DC-regulation; we understand it is what she mean, doesn't we? She continues; Additional mechanisms may allow local or network-wide changes in activity to be sensed through parallel pathways, generating a nested set of homeostatic mechanisms that operate over different temporal and spatial scales.

What kind of balance is homeostasis? And what is stress? It is about energyregulation or transfer. Free radicals. Relaxation.

Could there be a big scale protective mechanism at play, including both homeostasis and allostasis and every other regulation, that gives the best possible ground state energy? Subclinical simple partial siezures could be a protective measure to prevent siezures, but gives cognitive dysfunction? Correlations exist between meditation and incresed attentional parameters, but also to seizures. The adjustments of the balance can give disease? Can this be seen as consciousness of the body?

“Somehow the unstable stuff of which we are composed has learned the trick of maintaining stability” - Walter Cannon, The Wisdom of the Body, 1932.
This is remarkable, given that your brain is far more complex than the most complex machine. Usually the brain fixes itself. We usually not even think, or are conscious of that process of repair and growth going on. We are self-organizational, autonomous beings.
"unlike your car or your computer, your brain is not hard-wired but is constantly undergoing modifications to store information and adapt to changes in the environment. Nervous systems are thus faced with a fundamental problem: how to allow plastic mechanisms to shape their output and function, without compromising the stability and integrity of the underlying circuits that drive behavior. In other words, if brains are to work at all, they must be capable of assessing their own function and doing tune-ups on the fly."
A set of “homeostatic” plasticity mechanisms allow neurons to sense how active they are and to adjust their properties to maintain stable functions. = The sense of a self? This is like an apocrine communication, or a qualia?

So, what is this 'homeostasy'? - It acts to stabilize the activity of a neuron or neuronal circuit in the face of perturbations, such as changes in cell size or in synapse number or strength, that alter excitability.

So, in brain we have excitability and modulations; two ways to handle the firing at least.
"This review focuses on one form of homeostatic plasticity displayed by central glutamatergic neurons, called synaptic scaling, and its cellular and molecular mechanisms. A picture is beginning to emerge of how a cellular negative feedback system under the control of neuronal activity is implemented. Understanding when, where, and how homeostatic plasticity operates in the central nervous system is likely to generate important insights into how circuits adapt during experience-dependent plasticity, as well as the genesis of aberrant states, such as addiction or epilepsy, that involve adaptive plasticity or imbalances in synaptic excitation and inhibition. Maintaining stability in function [and structure] is a problem that permeates nearly every aspect of circuit development and plasticity."
The stability problem - matter maintenance - and changeable in memory.
Setting excitation and inhibition to the proper levels so that activity can propagate through a network without either dying out or increasing uncontrollably. Decoherence and coherence in play, see my essay.

Circuits/loops that have plastic synapses, as learnings that detect correlations between events in the environment and store these as changes in synaptic strength (LTP/LTD) (strengthen synaptic inputs that are effective at depolarizing the postsynaptic neuron and weaken inputs that are not, thus reinforcing useful pathways in the brain) or other cellular properties. Here the storage in spins, dots, qubits, magnetism is forgotten?

Synapses that are strengthened (LTP) become more effective at depolarizing the postsynaptic neuron and will continue to be strengthened in an unconstrained positive feedback cycle, eventually driving neuronal activity to saturation; the synapse-specificity of these synaptic plasticity mechanisms breaks down. Many forms of plasticity based on correlated activity of presynaptic and postsynaptic neurons that have now been described biologically are each likely to carry with them their own unique destabilizing influences. The nervous systems must have a matching set of plasticity mechanisms that counteract these destabilizing forces.
"if each neuron can sense how active it is and adjust its synaptic weights up or down to keep this activity close to some set-point value, network activity will remain stable in the face of correlation-based changes in synaptic strength or developmental changes in synaptic connectivity. Just such a mechanism was discovered in neocortical neurons and dubbed “synaptic scaling” because it was observed to globally scale all of a neuron’s synapses up or down in strength in the correct manners. This observation suggested that average neuronal activity, like many other physiological variables, is subject to classical homeostatic feedback control that stabilizes it around some set-point value."
So, then we have a primitive consciousness, a perception and sensing, a sampling of the environment AND inner environment in the cells.

Is homeostasy the same as consciousness (sensing)? And consciousness was depending on weak DC-currents in the brain. "At the minimum it likely requires that neurons sense some aspect of activity, integrate this measure over a time-step that is long (minutes to hours) relative to the time scale of information transfer (milliseconds to minutes), and adjust synaptic properties to minimize the difference between this value and an activity set-point ". Neurons, or synapses ARE really Selves?

This set-point value can be changed too, seen in addiction as instance. What aspect of neuronal or network activity is sensed by neurons?

Both panels represent the affective response to the presentation of a drug. (Top) This diagram represents the initial experience of a drug with no prior drug history, and the a-process represents a positive hedonic or positive mood state and the b-process represents the negative hedonic of negative mood state. The affective stimulus (state) has been argued to be a sum of both an a-process and a b-process.

Drug addiction represents an allostatic state in the brain reward system reflected in new reward set points, not only by dysregulation of reward circuits per se but also by the activation and recruitment of brain and hormonal stress responses. Allostasis is defined here as the process of achieving stability through change, and allostatic state is defined as a state of chronic deviation of the regulatory system from its normal operating (homeostatic) level.

Further issues important for the synchronity and coherence.
Networks of excitatory pyramidal and inhibitory GABAergic neurons generate robust spontaneous activity. When cultured hippocampal neurons are transfected with an inwardly rectifying potassium channel to hyperpolarize them and reduce firing, over time firing rates recover despite the continued expression of the channel. Cortical and hippocampal pyramidal neurons have a target firing rate, and synaptic strengths are regulated to maintain these rates relatively constant in the face of perturbations in input. Such “firing rate homeostasis” has not yet been directly demonstrated in the intact central nervous system.

Dendritic trees and interneurons (GABA) are also important for the stability.
Nonspecific binding in the brain or plasma is problematic to analyze, because it requires the researcher to scrutinize the various acceptations of the ubiquitous term "binding potential."

R. Becker, The Body Electric.

WalterB.Cannon,1963: Wisdom of the Body. W. W. Norton and Company, Inc.

Barry Dainton, 2010: Temporal Consciousness Stanford Encyclopedia 2010.

Dobrowolski A, Lolkema JS. 2009: Functional importance of GGXG sequence motifs in putative reentrant loops of 2HCT and ESS transport proteins. Biochemistry. 11;48(31):7448-56.

van Geest M, Lolkema JS. 1996 Membrane topology of the sodium ion-dependent citrate carrier of Klebsiella pneumoniae. Evidence for a new structural class of secondary transporters. J Biol Chem.11;271(41):25582-9.

Hudmon A.et al. 2005: A Mechanism for Ca2+/Calmodulin-Dependent Protein Kinase II Clustering at Synaptic and Nonsynaptic Sites Based on Self-Association. The Journal of Neuroscience, July 27, 2005, 25(30):6971-6983; doi:10.1523/JNEUROSCI.4698-04.2005.

Luke R. Johnson, Joseph E. LeDoux, and Valérie Doyère, 2009: Hebbian Reverberations in Emotional Memory Micro Circuits. Front Neurosci. 3(2): 198–205.

Kohonen,T.1982: Self-organized formation of topologically correct feature maps. Biological Cybernetics Volume 43, Number 1, 59-69, DOI:10.1007/BF00337288

George F Koob and Michel Le Moal, 2001: Drug Addiction, Dysregulation of Reward, and Allostasis Neuropsychopharmacology 24, 97-129. 10.1038/sj.npp.1395603

Joseph LeDoux, 2002, Synaptic Self: How Our Brains Become Who We Are.

Henry Stapp, 2007: Mindful Universe, Springer.


Turrigiano Gina G. 2008, The Self-Tuning Neuron: Synaptic Scaling of Excitatory Synapses. Cell. (3): 422–435. doi: 10.1016/j.cell.2008.10.008.

Yan C, Luo J.2010: An analysis of reentrant loops. Protein J.29(5):350-4.

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