Wednesday, 31 August 2011

Are Cortical Magnetic models ready for experimental verification ?

>>>> AUTHORS NOTE: This page provides the dipole mechanism, for evidence of neurodevelopmental dipole see HERE .<<<<<

Dipole neurology neurodevelopment theory could not have been built without existing works proposing the key mechanism that glial astrocytic cells could play in producing cortex wide magnetic fields, that is when the astrocytes are in the developmental state of a brain wide radial glia scaffold. Mainly pioneered by Marcos Banaclocha's Neuronal Activity Associated Magnetic fields (NAAMF) 2003, then expounded 2007

Following on, were increase in publications on biophysics of glia I refer to:  Ingber & Nunez, 2010 , Bokkon & Banaclocha, 2010 , Pereira 2012, Størmer & Laane, 2009Størmer et al,, 2011

Referring to the above authors, Prof Ingber of Caltech supports the proposal that glial magnetic models are a key missing link in brain function. His primary contribution is to focus on mathematical statistical models to calculate the aggregation of these proposed magnetic interactions.

His recent paper is the best physics based summary for magnetic models, and summarizes that enough theoretical work has been completed for lab verification to begin.

Pereira & Furlan provide a more neuroscience based overview for glial magnetic processes.

So the stage is already well set that Ca2+ waves can be a magneto-hydrodynamic fluid in adults. But the problem is the astrocytes are not connected across the brain for a wide range field, so only cortical column models are proposed by banachlocha. This following work provides experimental data which supports my prediction that calcium waves in radial Glial (early astrocytes) give rise to magnetic pulses across the entire cortex surface. i.e. This is a clear mechanism which can give rise to a cortex wide magnetic field in neurodevelopment.

Calcium Waves Propagate through Radial Glial Cells and Modulate Proliferation in the Developing Neocortex
Tamily A. Weissman1, Patricio A. Riquelme1, Lidija Ivic2, Alexander C. Flint2, Arnold R. Kriegstein, 1, 2, 3,
The developing brain has a stem cell derived scaffold throughout it called "radial glial" through which calcium ions pulse. This scaffold works just like the astrocytes in that it is an interconnected synctium for ions to pulse through and so macroscopic magnetic fields can arise. The mechanism is so similar that the radial glial eventually dissolves from stem cells to become astrocytes. The researchers already knew there was ion pulsing, in neurodevelopment but due to practical and ethical reasons they had to stimulate an entire hemisphere to pulse calcium ions by the method described below.

(A) Partial whole brains were prepared by removing ventral structures to open the ventricles, allowing for tissue perfusion and calcium indicator loading. Schematic shows partial whole-brain preparation and electrode placement. A, anterior; P, posterior; e, ganglionic eminence; v, ventricle; c, cortical anlage. (B) Low-magnifi cation view of Fluo-3 fl uorescence shows a mechanically stimulated calcium wave (electrode displacement of 5 μm) that propagates across the hemisphere. Higher-magnifi cation view shown in (C). Scale bar, 100 μm (B), 50 μm (C). This wave can be requested as a Supplemental Movie.

If this is not clear, what all this means is that the cortex dipole theory has a mechanism. If an entire magnetic field can pulse through each hemisphere there can be opposite poles in each hemisphere. Due to the tendency for magnetic fields to orientate the domains they influence into poles as large as the fields themselves, I predict the fields are ordering the ferroelectric components of the unmyelinated axons (microtubules and voltage gate potassium channels) into a dipole configuration.

A common objection raised to me in the past was that these glial pulses are too weak to overcome the earths static background field. After discussing this with various experts including Michael Persinger, I was informed a weak pulsed field has dynamics which can spike to overcome a more powerful static field. Lester ingber has also independently produced statistical mechanical mathematics in the paper linked above to describe this aggregation of magnetic fields in more detail than I could.

After all the controversy on the idea of a large scale quantum mind, there may still be some truth to aspects of the concept in neurodevelopment while neurons are not firing. As soon as immature neurons migrate along the scaffold and start to operate, this scaffold fades and so does the interconnected calcium ion field. Not surprising then why milk is so important for infants, but of all elements, why did nature choose calcium to produce magnetic fields? Its not hard to understand the principle.

Large magnetic fields can orientate larger biological structures together due to their ability to pass through liquids and biological material. This is one of the most highly effective ways to build a coherent structure nature could come up with. All that would be required is that developmental guidance has a means to resist these magnetic forces. The dipole neurology theory predicts that the immature ionotropic GABA (-ve chloride ion containing) and GLUTAMATE (+ve sodium ion gating) neurons are pulled apart as opposite charges in the magnetic field. This is proposed as the reason why these neurons are lateralized apart from each other at the brains temporal poles and why immature neurons have extra ion concentrations. In the paper we are reviewing the authors state

"Several neurotransmitters are present in the developing VZ at this stage and are possible candidates for a diffusible propagating signal, including glutamate, GABA (LoTurco et al., 1995), and taurine (Flint et al., 1998)"

Why then do the migrating neurons have adhesion proteins ?  These proteins dont actually have a mechanism to push the neurons up the scaffold. All they can do is release hold on the glial fiber temporarily. It is predicted that the adhesion are there to resist the magnetic field from the radial Glia. Nature then has a means to control the migration by modulating the degree of adhesion strength, perhaps by degree of Astrotactin release.

"quantitation of the dynamics of movement indicate that the leading process does not "pull" the neuron, rather the neuron moves by release and reformation of the adhesion junction beneath the cell soma. The nucleus remains in the posterior, moving with the soma, and does not undergo "nuclear migration"

As to calcium ions for a magnetic field, rather than say iron. Recent work from the genome centre using blue gene computers has dated the origin of glial cells at the same time neurons become ion based and replicated into large assemblies in bilateral sea creatures. Fish mostly. At this time the most abundant element in the ocean were salt (sodium and chlorine), organic iron and deposits of calcium carbonate that older sea creatures left behind after the Ordovician–Silurian extinction event of 440–450 Ma. It’s this abundance of calcium that was responsible for creatures developing bilateral (symmetrical) hard structures and then skeletons. There is simply an abundance of the material.

Ok enough background here are the results of the lab work. In the final figure, note the increasing size of the waves, through the entire hemisphere

Figure 1. 
Spontaneous Calcium Waves Propagate through the Embryonic Ventricular Zone
(A) Schematic drawing illustrates cortical anlage at embryonic day 16 (E16). LV, lateral ventricle; VZ, ventricular zone; CP, cortical plate; IZ, intermediate zone; SP, subplate; MZ, marginal zone.
(B–D) Individual spontaneous waves occurring within the VZ. (VZ is delineated at the left of each initial frame.) Waves initiate in VZ cells and propagate dorsally and medial/laterally. Scale bar, 25 μm.
(E) Selected individual cell transients (1–5) from (D) are represented as ΔF/F traces. Calcium levels in cells 4 and 5 (furthest from the initiation point) increase as levels in cells 1–3 decay.
(F) Some cells show spontaneously oscillating calcium levels, for example, cells c1 and c2 from (C) and cell d from (D).
(G) Spontaneous waves occur in a pattern of temporal clusters. This partially schematized image represents a three-dimensional field from an E16 coronal slice, with the ventricular surface sloping away in the lower part of the image. In this field, 11 waves were imaged in 8 min of observation. Shapes are drawn to approximate the spatial extent of each wave. The first four events (blue) occurred within the first minute, while five later events (black) were clustered within the fourth minute of observation. White events did not appear to occur within temporal clusters. Several events occurred in endfeet contacting the ventricular surface. Scale bar, 50 μm.
(H) Temporal clustering is shown in graphical form with the number of events plotted as a function of time (0.5 min bins).

Figure 7.
Radial Glial Calcium Waves May Be Involved in VZ Proliferation
(A) Cells that take up Lucifer yellow appear to be in S phase of the cell cycle. BrdU immunostain of VZ cells reveals several BrdU-positive, Lucifer yellow-positive cells. Scale bar, 20 μm.
(B) Developmental profile displaying changes in wave dynamics during the period of increasing neurogenesis in the VZ. In this three-dimensional graph, time is displayed along the x axis. Stimulated waves travel further (light gray bars) and involve more cells (dark gray bars) at later stages as shown. ATP sensitivity in the VZ also increases during this period (red bars). (E14 time point is with 100 μM, while E16 time point used 1 μM.) Spontaneous wave frequency also increases during the period of neurogenesis (blue bars). See text for numbers and error bars. (n.d., no data for this time point.)
(C) BrdU immunostain (green) with concanavalin A cellular stain (red) shows BrdU-positive VZ cells that are presumably in S phase of the cell cycle. Such images were used for quantification of proliferation experiments. Scale bar, 30 μm.
(D) In organotypic slice culture, the ATP receptor antagonist suramin (50 μM) significantly decreased VZ cell proliferation at E16 (dark gray bars), when VZ calcium waves are robust, shown as the percentage of BrdU-positive cells (normalized to control) that incorporated BrdU in S phase during a 1 hr pulse. However, at E14 (light gray bars), when waves are small and ATP sensitivity in the VZ is very low, suramin had no effect on proliferation. As expected, proliferation is decreased at both ages in the presence of cytosine arabinoside (Ara-C, 20.5 μM), an antimitotic agent.
(E) The phospholipase C activator PMT (200 ng/mL) rescues the antiproliferative effect of suramin.