måndag 7 mars 2011

Neural communication outside synapses II. Weak electric fields.

Weak electrical fields in the brain help neurons fire together
Extracellular electric fields (DC-currents) exist throughout the living brain. Their distant echoes can be measured outside the skull as EEG waves.The perpetual fluctuations of these extracellular fields are the hallmark of the living and behaving brain in all organisms, and their absence is a strong indicator of a non-functional brain.
Our results support the notion that ephaptic potentials induced by oscillating electric fields present throughout the gray matter serve to synchronize neuronal activity with little regard to whether excitatory or inhibitory. Such synchronization may have a substantial effect on neural information processing and plasticity.
Endogenous electric field activity in the living brain typically induces extracellular voltage changes less than 0.5 mV and fields under 5 mV mm−1
This is often in the 1Hz region or below, but can seldom climb to 30 Hz. Induction of an action potential requires about 25 mV. Coupled to Na-receptors (and mechanosensitive receptors?).

External electric fields.
Can external electric fields have similar effects on the brain? Indeed, physics dictates that any external field will impact the neural membrane. Importantly, though, the effect of externally imposed fields will also depend on the brain state, and on which brain area is targeted. During epileptic seizures, pathological fields can be as strong as 100 millivolts per millimeter - such fields strongly entrain neural firing and give rise to super-synchronized states, which suggests that electric field activity - even from external fields - in certain brain areas, during specific brain states, may have strong cognitive and behavioral effects.

Brain interactions? Thunder? Telepathy?
Jazz musicians jaming togeteher get synchronized brainwaves? MS patinets have often reported extraordinary sensitivity for thunder, or car drivings, already as kids. Are their brains more sensitive to induced electricity? As developing tissues are? This is also at the core of meridian work.

"I firmly believe that understanding the origin and functionality of endogenous brain fields will lead to several revelations regarding information processing at the circuit level, which, in my opinion, is the level at which percepts and concepts arise," Anastassiou says. "This, in turn, will lead us to address how biophysics gives rise to cognition in a mechanistic manner - and that, I think, is the holy grail of neuroscience."

The background.

Currents from synaptic events or action potentials can enter at one location in a neuron and leave at another, completing a loop through the extracellular space and giving rise to extracellular potentials. Temporally prolonged synaptic currents are thought to be more significant. The effects of synaptically induced extracellular potentials are known to be responsible for mediating population responses that lead to large-scale brain phenomena that can be recorded with electroencephalography (EEG) and magnetoencephalography (MEG) (Jefferys 1995). Becker showed that a transversed Dc-potential in the brain could induce anesthesia effects.

The brain is enveloped in countless overlapping electric fields, generated by the neural circuits of scores of communicating neurons. The 'talk' = modulation of dendritic (analog) membranes and their fields. The fields were once believed to be an epiphenomenon, a 'bug' of sorts, occurring during neural communication, but they may, in fact, represent an additional form of neural communication. "So far, neural communication has been thought to occur at synapses. Our work suggests an additional means of neural communication through the extracellular space independent of synapses". They focused on strong but slowly oscillating fields, called local field potentials (LFP), that arise from neural circuits composed of just a few rat brain cells.

While active neurons give rise to extracellular fields, the same fields feed back to the neurons and alter their behavior, even though the neurons are not physically connected—a phenomenon known as ephaptic (or field) coupling. This energy field “connection” could be another mode of coordination within the brain – one separate from the usual neuron-synapse channels. However, in a very wide view of recent biophysics, this study joins the research on the trail of how the brain seems to so rapidly coordinate diverse areas into what is called “thinking” (or consciousness, or intelligence, or whatever). Many neuroscientists believe that the relatively slow and almost infinitely intertwined activity of neurons and synapses doesn’t quite add up to the speed and efficiency of thought. They are looking at other possibilities, be it quantum effects or endogenous brain fields. It could be a very important direction for research, but it’s just starting (the nerve action model is one thing to reconsider-HH model old? It is restricted to dissipative electrical phenomena and considers nerve pulses exclusively as a microscopic phenomenon. A simple thermodynamic model that is based on the macroscopic properties of membranes allows explaining more features of nerve pulse propagation including the phenomenon of anesthesia that has so far remained unexplained).

Ephaptic interactions occur in neurons that are coupled by current loops in the extracellular space. Such interactions are mostly negligible in comparison to chemical and electrical synaptic interactions (chemical synapses or electrotonic gap junctions) due to the relatively large area of the extracellular space. The functional significance of ephaptic coupling is, therefore, often not considered. Certain physical situations, such as close packing of neurons, however, may increase the efficacy of ephaptic interactions.

There is also a fact that nerves never enter cells; nerve endings always end in extracellular space. No output would then be possible? (There are specialized proteins for the junction nerve-cell).

Density and time gives synchronity?

In experimental conditions that increase the axial resistance of the extracellular space surrounding two fibers, as well as in certain pathological conditions involving demyelination and nerve compression, the activity of one fiber can be shown to influence the activity of the other fiber through extracellular current loops (Jefferys 1995). Such an interaction was coined by Arvanitaki (1942) as ephaptic, from the Greek “touching onto,” contrasting with synaptic, or, “touching together.”

These fields are particularly strong and robustly repetitive in specific brain regions such as the hippocampus, which is involved in memory formation, and the neocortex, the area where long-term memories are held, or the mammalian olfactory nerve (axons lack myelin, and they are arranged in densely packed fascicles), tinnitus. Spontaneous rhythmic neuronal activity is generated in the developing vertebrate nervous system (robust rhythmic patterns in the absence of synaptic activity). Cardiac cells - the extracellular junctional cleft space between neighboring cells is very narrow and tortuous, it might act as a microdomain for ionic concentrations and the electric potential. In this microdomain, ionic concentrations and the electric potential might vary drastically and rapidly enough to influence action potential propagation or perhaps conduct an electrical signal from one cell to the next.
Ephaptic coupling increases propagation velocity at low gap junctional conductivity while it decreases propagation at higher conductivities. We also find that conduction velocity is relatively insensitive to gap junctional coupling when sodium ion channels are located entirely on the cell ends and cleft space is small.

The phasetuning- curve involve specific ephaptically mediated hyperpolarizing and depolarizing currents (dendrite- dendrite interaction): Ephaptic coupling might positively affect auditory coincidence detection allowed the neuron to respond more precisely.

More local consequences of extracellular potentials (i.e. the direct influence of one neuron on another via ephaptic coupling) have been observed in a few systems, such as the Mauthner cells in the motor system of the teleost fish, the Purkinje cells of cerebellum; possibly the existence of dendrodendritic synapses between mitral cells and granule cells in olfactory cells; among pyramidal cells in hippocampus greatly enhances the synchrony of their firing.

Ephaptic Interactions in the Mammalian Olfactory System. If olfactory discrimination is dependent on coding expressed by the temporal order of action potentials, ephaptic coupling will influence discrimination by affecting the frequency of action potentials in neighboring axons and by inducing synchrony in their firing. This synchrony may be involved in generating oscillations in the patterns of input to the olfactory bulb, and these oscillations may be a critical element of the olfactory code. Bokil et al 2001 JNeurosci, 2001, 21:RC173 (1–5).

Binczak, 2001: Since myelinated nerve fibers are often arranged in bundles, this model is used to study ephaptic (nonsynaptic) interactions between impulses on parallel fibers, which may play a functional role in neural processing. Smooth nerve bers which are described by nonlinear partial di fferential equations (nonlinear reaction di ffusion equations), but many nerve fibers are discrete, periodic structures, comprising active nodes separated by sections of nerve that are insulated by myelin; the wave of activity jumps from one node to the next and can be described by nonlinear di erence-di erential equations (domino-effect). Myelinated nerve structures are useful because they allow an increase in the speed of a nerve impulse while decreasing the diameter of the nerve fiber; thus the motor nerves of vertebrates which are about the same diameter as a squid giant axon comprise several hundred individual fibers, each serving as an independent signaling channel + need less energy. Another feature of myelinated nerves is the possibility of failure when the distance (or electrical resistance) between the active nodes becomes too large. We show here that both of these phenomena are influenced by ephaptic coupling.
The phenomena of impulse synchronization due to ephaptic interactions in the saltatory and continuum limits also discussed.

Membrane architechture in myelinated neurons: The outer surface of the myelin sheath was well visualized in electron micrographs of replicas and the distribution of its cytoplasm-containing portions could be analysed. Numerous caveolae, probably representing the surface stomata of endo- or exocytotic vesicles were found on the plasmalemmal surface overlying organelle-rich cytoplasmic regions. Membrane specializations of the tight-junction type were found at the outer and inner mesaxons of the myelin sheath as well as at the Ranvier node and Schmidt-Lanterman incisures. Presuming that so-called leakiness is related to the junctional morphology, these junctions would be classified as moderately leaky. The morphological features of the Schwann-cell nuclear envelope were essentially as described for other mammalian cells.

Axon-glia dance: Myelinated nerve fibers are designed in an optimal manner which requires tuning of conduction time with millisecond precision. This involves the highly coordinated differentiation of axons and myelin-forming glial cells; the nature of the signals involved in this axon–glial cell dance are beginning to be elucidated.

Extremely weak extracellular fields have effects?
An "unexpected and surprising finding was how already very weak extracellular fields can alter neural activity. For example, fields as weak as one millivolt per millimeter robustly alter the firing of individual neurons, and increase the so-called "spike-field coherence" - the synchronicity with which neurons fire with relationship to the field. In mammalian brain, extracellular fields may easily exceed two to three millivolts per millimeter. Our findings suggest that under such conditions, this effect becomes significant."

Increased spike-field coherency may substantially enhance the amount of information transmitted between neurons as well as increase its reliability. Moreover, it has been long known that brain activity patterns related to memory and navigation give rise to a robust LFP and enhanced spike-field coherency.

"We believe ephaptic coupling does not have one major effect, but instead contributes on many levels during intense brain processing."

Ephaptic coupling of cortical neuronsSimultaneous recordings from up to 12 electrodes inside and outside a single neuron in rat slice during intra- and extracellular stimulation. From"Ephaptic coupling of cortical neurons."
  • Costas A Anastassiou, Rodrigo Perin, Henry Markram, Christof Koch. Ephaptic coupling of cortical neurons. Nature Neuroscience, 2011; 14 (2): 217 DOI: 10.1038/nn.2727
The electrochemical processes that underlie neural function manifest themselves in ceaseless spatiotemporal field fluctuations. However, extracellular fields feed back onto the electric potential across the neuronal membrane via ephaptic coupling, independent of synapses. The extent to which such ephaptic coupling alters the functioning of neurons under physiological conditions remains unclear. To address this question, we stimulated and recorded from rat cortical pyramidal neurons in slices with a 12-electrode setup. We found that extracellular fields induced ephaptically mediated changes in the somatic membrane potential that were less than 0.5 mV under subthreshold conditions. Despite their small size, these fields could strongly entrain action potentials.
These were changes in the membrane potential Vm along an extended neuronal cable caused by an external electric field and are a simple consequence of Kirchhoffs’ circuit laws. Their amplitude was below 0.5 mV, consistent with theoretical estimates20. These potentials remained undiminished at frequencies up to 100 Hz and were independent of synaptic input, as all receptors were pharmacologically blocked. Given the small amplitude of ephaptic potentials relative to the spiking threshold that is approximately 25 mV above rest, it is not clear how they could have any substantial role in the life of a spiking neuron. To evaluate whether they can, we induced pyramidal neurons to fire action potentials at 2–4 Hz. by direct current injection. Indeed, the modest (in amplitude) electric field did not trigger any additional action potentials. However, it did induce substantial shifts in the timing of these action potentials. Even very small and slowly changing fields that triggered Ve changes under 0.2 mV led to phase locking of spikes to the external field and to a greatly enhanced spike-field synchrony. This high sensitivity of spike timing to small, but persistent, oscillations that act throughout a volume needs to be contrasted with the intrinsic, that is, nonsynaptic, noise in layer 5 pyramidal neurons of 0.2–0.4 mV46 and to the much larger noise if synaptic background activity is taken into account. The oscillations causing the greatest effect (1 Hz) mimicked the frequency of cortical slow waves, a common rhythm observed during natural sleep and under anesthesia. Although these effects persisted for frequencies up to 8 Hz, that is, the theta bandwidth, they became gradually smaller as the field frequency increases. At 30 Hz, only the largest external field still had an effect.
Individual neurons can have frequency preferences that enable them to respond best to inputs in a narrow frequency window47. In the presence of a suprathreshold intracellular direct current input, Ve oscillations might induce such frequency-specific spiking. However, when examining the Vm response induced by the suprathreshold dc input without an extracellular field (control experiments), the resulting Vm fluctuations were substantial and their amplitude greatly exceeds that induced through ephaptic coupling. Thus, membrane resonance to weak oscillatory extracellular stimuli seems to be an implausible mechanism given the strong intracellular fluctuations induced by direct intracellular dc injection.
An alternative explanation is that, for slow stimuli, the neural membrane can be described by a simple phenomenological model with constant firing threshold. If it takes synaptic input 100 ms to reach a 10-mV spike threshold, then a 0.5-mV ephaptic potential will phase advance the next spike by 5 ms. An oscillatory extracellular field along a neuron receiving strong intracellular input leads to periodic polarization of the membrane and the emergence of spike-phase preferences. For faster extracellular stimuli, a possible combination of various spiking-associated currents and differential entrainment of the different neural compartments leads to the gradual loss of such spike-phase preference.
Our results suggest that periodic membrane polarization resulting from ephaptic coupling to the slow frequencies of the LFP define temporal windows of enhanced excitability across the cells experiencing this field. Such phase coding with reference to the slow (1–8 Hz) ongoing LFP signal has been shown to provide substantial enhancement of mutual information in coexistence with other codes, such as spatial and temporal spike patterns, as well as increased robustness. Using a setup that allowed us to control and measure electric fields and potentials at up to 12 locations inside and outside an individual neuron at high fidelity, we examined the manner in which an external field leads to phase locking of individual neurons, as well as spike synchrony among quartets, triplets and pairs of nearby neurons.
How relevant is ephaptic coupling, obtained here under artificial (slice) conditions, to the living brain? The amplitudes of our extracellular potentials (up to 0.6 mV) and fields (up to 6 mV mm−1) were comparable to the amplitudes of LFPs measured under natural conditions. Furthermore, our changes in SFC were as large, or larger, than those observed in cortex. For instance, successful memory formation in humans is predicted by a tight coordination of spike timing in hippocampal neurons to the local theta oscillation, with SFC increase of approximately 50% compared to unsuccessful trials. These changes are entirely consistent with our measured ephaptic coupling to the LFP and were associated with Ve and E amplitudes of 0.1 mV and 1 mV mm−1. Finally, the fields induced in our experiments were comparable to fields applied outside the skull that have been shown to alter cognitive processes in humans.

Google search Binczak: Ephaptic coupling of myelinated nerve fibers

Jefferys, J.G.R. (1995). Nonsynaptic modulation of neuronal activity in the brain: Electrical currents and extracellular ions. Physiological Reviews, 75, 689-723.

2 kommentarer:

  1. Ulla,

    You have so much in these two posts. Did you catch this result:


    Interesting that the flies can distinguish Hydrogen and Deuterium- I never thought much of the idea it was simply the shape of molecules nor that artificial ones to mimic flavor could have not hidden ill effects.

    I like the stages of deeper processing- the long and short terms memory of it all in terms of DNA and so forth. In the moment or brain cells light up at the hint of rumors and chatter like they crave salty sugar when in the guardians of the conversation, back and forth on the next deeper level they are saying " Nevermind this, Let us all push the host to bring us a good steak!"

    Now, there can be more levels beyond ideas of quanta and so on with some sort of laws that gives persistence of the real. Which on the average is our true center of consciousness?

    Certainly we can look at disease as containing germs as the cause, or that germs only thrive in broken bodies. Too little is know about the end of cell life. While we may be able to extend it by repair of the teleomeres it may result in more tumor growth as a recent article said.

    As in my last post, where I hinted as more ideas on the deeper nature of consciousness it came from a dream where the nerves said "you are sick, forget that and give us steak!"
    And I realized that some of us think mainly on one of the other of these levels- and we cannot always understand even in ourselves what is on a higher level (say of theory) or if a dream makes sense looking down on it, always. But from all levels the theme and dream can persist as to some urgency or decision coming to consciousness. But what this means I am not clear other than it hints at a more profound level of being and perception than we now imagine. I doubt there is a simple magic fix that only communicates on the quantum level and not in our sense of self itself between all our levels. Synaspes as the mediator are but the lowest level of what makes our mental effects.

    The PeSla

  2. Thanks for your long comment.

    Dreams talk sense, although they may seem bizarre. It is the body talking to our minds, the subconsciousness.

    It is hopeless to discuss consciousness without a proper definition of words behind. I like Damasios therminology. TGD talks of conscious processes also for unconscious things, as the odors. I can understand that well, and it makes sense. Why interrupt the conscious process with words? Instead we canmore use the word aware for our eg. conscious processes inour brains. Jung talks of 'breaking the surface' and maybe that is what it is about?

    Dreams telling us to forget we are sick and command us to have steaks, tell us we must change our metabolism. And it also brings forth the importance of our thoughts,that Damasio showed was real, and gave real resposes. If we think we are sick, then we are sick.

    To forget and forgive is important for this reason. To let things be as they are.

    DC-electricity has long been one of my deep interests. It gives the conscious mind. It also gives the negentropy maximation, and directs regeneration. It is fixed beyond our reality, in the bosonic world.

    Synapses are about our physical body. They are the wire only? The search for a mechanistic wiev will terminate on the unknown world beyond?