Slow periodic activity in the longitudinal hippocampal slice can self‐propagate non‐synaptically by a mechanism consistent with ephaptic coupling
Slow oscillations are a standard feature observed in the cortex and the hippocampus during slow wave sleep. Slow oscillations are characterized by low‐frequency periodic activity (<1 Hz) and are thought to be related to memory consolidation. These waves are assumed to be a reflection of the underlying neural activity, but it is not known if they can, by themselves, be self‐sustained and propagate. Previous studies have shown that slow periodic activity can be reproduced in the in vitro preparation to mimic in vivo slow oscillations. Slow periodic activity can propagate with speeds around 0.1 m s−1 and be modulated by weak electric fields. In the present study, we show that slow periodic activity in the longitudinal hippocampal slice is a self‐regenerating wave which can propagate with and without chemical or electrical synaptic transmission at the same speeds. We also show that applying local extracellular electric fields can modulate or even block the propagation of this wave in both in silico and in vitro models. Our results support the notion that ephaptic coupling plays a significant role in the propagation of the slow hippocampal periodic activity. Moreover, these results indicate that a neural network can give rise to sustained self‐propagating waves by ephaptic coupling, suggesting a novel propagation mechanism for neural activity under normal physiological conditions.
Abstract isn't so flamboyant as the linked article
Does anyone know, how does the strength of these fields compare to the strength of the field in the brain from a wifi router at a reasonable distance? Why doesn’t all the comms gear mess with our thought processes?
as this study shows, as well as others, electric fields do "mess up" with individual synaptic transmission. nature has evolved action potentials as a reliable way to propagate signals in the presence of the myriad sources of electromagnetic radiation on earth. They can be disrupted by appropriately high stimulation such as with TMS . Most likely, the radiation sources that we use every day, phones computers etc do have some effect in neurotransmission but those random failures are probably too few (and too random) to matter significantly or systematically.
Neuroscience PhD student here. The skull acts as a low-pass filter. EEG recordings are typically low pass filtered at 70Hz or lower for example. This is why you can’t decode eg speech from a EEG: the neural encoding is at a higher frequency band than can be recorded. Even though the signal is much stronger, digital comms equipment is orders of magnitude higher in frequency and does not penetrate the skull well.
fMRIs use a crazy strong magnetic field—typically >= 3 Tesla. The signal that is measured is not electrical but rather the blood oxygen level. Effectively, this is a correlate of the metabolic expenditure of nearby neurons. Wass it is also like a low-pass filter except here it’s more like 0.5 Hz or slower. On the plus, you get much improved spatial resolution
MRIs use two magnetic fields, a static one and a dynamic one. And they use a radio signal according to the larmor frequency to excite the spin of the atoms. I was wondering about that radio signal component.
This has very little relevance to the topic at hand as these refer to electroencephalogram measurements taken through a skin (scalp) patch and conductive gel.
Empirically, we'd want data on how corresponding electromagnetic pulses would affect brain activity -- there should be resonance effects, once the amplitude is high enough.
Looking at the paper [0], particularly Figure 4, it looks like they cut slices then stick them back together again. This allows the signal to propagate (4.B).
But when a gap of 400 microns is added (4.C), the signal doesn't propagate.
I'm sure that the actual cutting causes some damage, and perfect realignment is unlikely, but I'm not sure how this is conclusive of ephaptic coupling, or how it eliminates the possibility of electrical or chemical communication by synapse, gap junction, or axonal transmission.
A synaptic cleft is like 40 nm, or 10,000x smaller than 400 microns, so it seems the scales of typical communication are enough orders of magnitude smaller to be an implausible explanation?
If the signal transmission worked at 400 microns, I would say that your feature size argument would be a good reason to consider other explanations, but they explicitly show that such a gap prevents the signal from being transmitted.
Instead, the transmissible gap is poorly characterized—-they cut then stick the slices back together. Depending on how clean the cut is, the gap could be quite small. Yet they argue that this unknown small distance (which presumably still contains a fluid interface) is enough to eliminate the usual explanations. That argument feels undersupported to me.
Ah, I was under the assumption that 400 microns was implied to be at least within an order of magnitude of the threshold, so for example I assumed the signal transmission worked at at least 40 microns, which is still 1000x the synaptic cleft. If there's no information about where the cut-off is, only some upper limit, perhaps even due to the lack of precision in the technique itself, then this does seem pretty questionable, indeed.
Or, furthermore, by standard induction, or by standard conduction via the extracellular matrix (assuming the ECM can deal w/400microns and axons/dendrites cannot—idk if this holds)
When the electrical field potential changes, it changes the probability of neural firing. It's called ephatic coupling. Brain waves (local field potential) aren't just the measured average of the neural firing, but are a signal propagating force. This supports synchronization through entrainment and other resonance effects that are well characterized. Not sure why this is new, but it is great to see it in the news.
I’m not sure how many people would agree with the characterization of brain waves as a signal propagating force.
I think you’re probably right that they are, but there’s still an on-going and fairly contentious debate over the extent to which the LFP reflects vs. changes transsynaptic currents.
Very different. Retinal waves are a developmental phenomena and use action potentials for propagation. The study at hand attempts to disrupt all action potential transmission.
I wonder if this validates the Orchestrated Objective Reduction theory of consciousness pioneered by Roger Penrose and Stuart Hameroff. Seems like it would.
A bit technical, but some of the most vocal critics of Orch-OR claimed there was no way that quantum states could orchestrate across synapses or between neurons. This quite interesting finding argues otherwise.
I don't see how this enables any orchestration that other signals do not. There's still decoherence. It must have been among the weakest objections to Orch-OR. Knocking down the weakest counter-argument (which sounds like a strawman) doesn't really bolster the hypothesis in any way.
it means that neurons can 'transmit' a spike to their immediately neighboring neurons even without chemical synaptic transmission (which is the norm). i cant think of a relation to sleep but there could be one.
>Until now, there were three known ways that neurons “talk” to each other in the brain: via synaptic transmission, axonal transmission and what are known as “gap junctions” between the neurons.
I know about chemical synapses (the "usual" synapses with gain, and which we model with weights in artificial neural networks, and which transmit information in forward mode), I also know about electrical synapses (fast, no gain, bidirectional, possibly mediator of the backpropagation signal?) but I don't know what they refer to with "axonal transmission" ? surely they don't just mean pulse propagation along the axon, can someone point me to the accepted mechanism of axonal transmission across neurons? from cell body to synapse is just transmission line along the same neuron...
also correlation is not necessarily propagation, consider for example shining a laser dot on a distant wall, and rotating the beam such that the spot moves faster than light: this is perfectly possible, but no physical signal is moving faster than light, rather the dot at some initial time and the dot at a later time are correlated, but are both the result of a laser reflecting of a rotating mirror.
in order to eliminate a mutual cause, you dont make a local cut in some neuronal tissue, you fully separate the tissue, and then measure their electrical activity (preferably optically using a nematic liquid crystal as they used in the past to inspect voltage levels on chips under microscopes) while mounted on micron precision translation stage, and starting from a distance, slowly have the samples approach and measure their correlation, and do the same experiment without a neuron culture, because the correlation may be due to stray electric fields from the environment (another common cause, like the laser for the lightspeed dots)
use 2 different wavelengths (and corresponding filters at the detectors) of light to measure the optical activity of the nematic liquid crystal sensors, in order to make sure no light is leaking through...
>Since some axons are on the order of meters long, neurons cannot rely on diffusion to carry products of the nucleus and organelles to the end of their axons.
and:
>Vesicular cargoes move relatively fast (50–400 mm/day) whereas transport of soluble (cytosolic) and cytoskeletal proteins takes much longer (moving at less than 8 mm/day).
note that the flow of material in axonal transport is retrograde (i.e. in the opposite direction of pulse transmission), so any feedback, adjoint sensitivity or backpropagation signal - if it exists - to implement Automatic Differentiation in a physical manner, might move at such speeds. I don't know the typical axon lengths (please tell me if you know or can refer me to measured distributions of axon length), but this maximum of about 1000mm implies 125 days (8mm/day) or 2.5 days (400mm/day). If we assume the dimension of the brain as a typical axon length i.e. 10cm = 100mm then this becomes 12.5 days (400mm/day) and 0.25 days or six hours (8mm/day). For 1cm we have 30 hours (8mm/d) and 36 minutes (400mm/d). For 1cm to 10cm typical axon lengths and shorter indeed seem like the kind of time frame of learning, i.e. the weights may be modified during sleep, and the delay line of materials undergoing axonal transport in each axon contain echoes or memories of synaptic activity during the day.
Abstract
Slow periodic activity in the longitudinal hippocampal slice can self‐propagate non‐synaptically by a mechanism consistent with ephaptic coupling
Slow oscillations are a standard feature observed in the cortex and the hippocampus during slow wave sleep. Slow oscillations are characterized by low‐frequency periodic activity (<1 Hz) and are thought to be related to memory consolidation. These waves are assumed to be a reflection of the underlying neural activity, but it is not known if they can, by themselves, be self‐sustained and propagate. Previous studies have shown that slow periodic activity can be reproduced in the in vitro preparation to mimic in vivo slow oscillations. Slow periodic activity can propagate with speeds around 0.1 m s−1 and be modulated by weak electric fields. In the present study, we show that slow periodic activity in the longitudinal hippocampal slice is a self‐regenerating wave which can propagate with and without chemical or electrical synaptic transmission at the same speeds. We also show that applying local extracellular electric fields can modulate or even block the propagation of this wave in both in silico and in vitro models. Our results support the notion that ephaptic coupling plays a significant role in the propagation of the slow hippocampal periodic activity. Moreover, these results indicate that a neural network can give rise to sustained self‐propagating waves by ephaptic coupling, suggesting a novel propagation mechanism for neural activity under normal physiological conditions.
Abstract isn't so flamboyant as the linked article
Does anyone know, how does the strength of these fields compare to the strength of the field in the brain from a wifi router at a reasonable distance? Why doesn’t all the comms gear mess with our thought processes?
as this study shows, as well as others, electric fields do "mess up" with individual synaptic transmission. nature has evolved action potentials as a reliable way to propagate signals in the presence of the myriad sources of electromagnetic radiation on earth. They can be disrupted by appropriately high stimulation such as with TMS . Most likely, the radiation sources that we use every day, phones computers etc do have some effect in neurotransmission but those random failures are probably too few (and too random) to matter significantly or systematically.
here is a recent review: http://sci-hub.tw/https://www.sciencedirect.com/science/arti...
Neuroscience PhD student here. The skull acts as a low-pass filter. EEG recordings are typically low pass filtered at 70Hz or lower for example. This is why you can’t decode eg speech from a EEG: the neural encoding is at a higher frequency band than can be recorded. Even though the signal is much stronger, digital comms equipment is orders of magnitude higher in frequency and does not penetrate the skull well.
What about the radio signal used for MRI imaging, is it blocked by the skull as well? Or is it just strong enough to be able to penetrate the skull?
fMRIs use a crazy strong magnetic field—typically >= 3 Tesla. The signal that is measured is not electrical but rather the blood oxygen level. Effectively, this is a correlate of the metabolic expenditure of nearby neurons. Wass it is also like a low-pass filter except here it’s more like 0.5 Hz or slower. On the plus, you get much improved spatial resolution
MRIs use two magnetic fields, a static one and a dynamic one. And they use a radio signal according to the larmor frequency to excite the spin of the atoms. I was wondering about that radio signal component.
I can't say with 100% certainty that it would have no effect, but the following may be of use:
Frequency of Brain Waves
State Frequency range State of mind
Delta 0.5Hz–4Hz Deep sleep
Theta 4Hz–8Hz Drowsiness (also first stage of sleep)
Alpha 8Hz–14Hz Relaxed but alert
Beta 14Hz–30Hz Highly alert and focused
This has very little relevance to the topic at hand as these refer to electroencephalogram measurements taken through a skin (scalp) patch and conductive gel.
Empirically, we'd want data on how corresponding electromagnetic pulses would affect brain activity -- there should be resonance effects, once the amplitude is high enough.
Looking at the paper [0], particularly Figure 4, it looks like they cut slices then stick them back together again. This allows the signal to propagate (4.B).
But when a gap of 400 microns is added (4.C), the signal doesn't propagate.
I'm sure that the actual cutting causes some damage, and perfect realignment is unlikely, but I'm not sure how this is conclusive of ephaptic coupling, or how it eliminates the possibility of electrical or chemical communication by synapse, gap junction, or axonal transmission.
[0] https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP276904
A synaptic cleft is like 40 nm, or 10,000x smaller than 400 microns, so it seems the scales of typical communication are enough orders of magnitude smaller to be an implausible explanation?
If the signal transmission worked at 400 microns, I would say that your feature size argument would be a good reason to consider other explanations, but they explicitly show that such a gap prevents the signal from being transmitted.
Instead, the transmissible gap is poorly characterized—-they cut then stick the slices back together. Depending on how clean the cut is, the gap could be quite small. Yet they argue that this unknown small distance (which presumably still contains a fluid interface) is enough to eliminate the usual explanations. That argument feels undersupported to me.
Ah, I was under the assumption that 400 microns was implied to be at least within an order of magnitude of the threshold, so for example I assumed the signal transmission worked at at least 40 microns, which is still 1000x the synaptic cleft. If there's no information about where the cut-off is, only some upper limit, perhaps even due to the lack of precision in the technique itself, then this does seem pretty questionable, indeed.
Or, furthermore, by standard induction, or by standard conduction via the extracellular matrix (assuming the ECM can deal w/400microns and axons/dendrites cannot—idk if this holds)
When the electrical field potential changes, it changes the probability of neural firing. It's called ephatic coupling. Brain waves (local field potential) aren't just the measured average of the neural firing, but are a signal propagating force. This supports synchronization through entrainment and other resonance effects that are well characterized. Not sure why this is new, but it is great to see it in the news.
Here is the reference: https://www.nature.com/articles/nn.2727
I’m not sure how many people would agree with the characterization of brain waves as a signal propagating force.
I think you’re probably right that they are, but there’s still an on-going and fairly contentious debate over the extent to which the LFP reflects vs. changes transsynaptic currents.
Is this different from retinal waves? https://en.wikipedia.org/wiki/Retinal_waves
Very different. Retinal waves are a developmental phenomena and use action potentials for propagation. The study at hand attempts to disrupt all action potential transmission.
Does the method that Transcranial magnetic stimulation effects neurons relate to this out of interest?
I wonder if this validates the Orchestrated Objective Reduction theory of consciousness pioneered by Roger Penrose and Stuart Hameroff. Seems like it would.
What does this have to do with supposed qubits inside neurons?
A bit technical, but some of the most vocal critics of Orch-OR claimed there was no way that quantum states could orchestrate across synapses or between neurons. This quite interesting finding argues otherwise.
I don't see how this enables any orchestration that other signals do not. There's still decoherence. It must have been among the weakest objections to Orch-OR. Knocking down the weakest counter-argument (which sounds like a strawman) doesn't really bolster the hypothesis in any way.
I noted this on the other thread about this discovery:
I wonder if this might be a basis for a biological means for "backpropagation"?
Is this really new? I always thought that this was essentially the implication of the discovery of standing-waves in the brain
what does that mean? is that a form of explanation for why we are more creative or able to solve problems in our sleep (or after sleep)?
it means that neurons can 'transmit' a spike to their immediately neighboring neurons even without chemical synaptic transmission (which is the norm). i cant think of a relation to sleep but there could be one.
never reported publicly anyway...underpinning of psychic phenomena perhaps?
>Until now, there were three known ways that neurons “talk” to each other in the brain: via synaptic transmission, axonal transmission and what are known as “gap junctions” between the neurons.
I know about chemical synapses (the "usual" synapses with gain, and which we model with weights in artificial neural networks, and which transmit information in forward mode), I also know about electrical synapses (fast, no gain, bidirectional, possibly mediator of the backpropagation signal?) but I don't know what they refer to with "axonal transmission" ? surely they don't just mean pulse propagation along the axon, can someone point me to the accepted mechanism of axonal transmission across neurons? from cell body to synapse is just transmission line along the same neuron...
also correlation is not necessarily propagation, consider for example shining a laser dot on a distant wall, and rotating the beam such that the spot moves faster than light: this is perfectly possible, but no physical signal is moving faster than light, rather the dot at some initial time and the dot at a later time are correlated, but are both the result of a laser reflecting of a rotating mirror.
in order to eliminate a mutual cause, you dont make a local cut in some neuronal tissue, you fully separate the tissue, and then measure their electrical activity (preferably optically using a nematic liquid crystal as they used in the past to inspect voltage levels on chips under microscopes) while mounted on micron precision translation stage, and starting from a distance, slowly have the samples approach and measure their correlation, and do the same experiment without a neuron culture, because the correlation may be due to stray electric fields from the environment (another common cause, like the laser for the lightspeed dots)
use 2 different wavelengths (and corresponding filters at the detectors) of light to measure the optical activity of the nematic liquid crystal sensors, in order to make sure no light is leaking through...
According to wikipedia https://en.wikipedia.org/wiki/Axonal_transport :
>Since some axons are on the order of meters long, neurons cannot rely on diffusion to carry products of the nucleus and organelles to the end of their axons.
and:
>Vesicular cargoes move relatively fast (50–400 mm/day) whereas transport of soluble (cytosolic) and cytoskeletal proteins takes much longer (moving at less than 8 mm/day).
note that the flow of material in axonal transport is retrograde (i.e. in the opposite direction of pulse transmission), so any feedback, adjoint sensitivity or backpropagation signal - if it exists - to implement Automatic Differentiation in a physical manner, might move at such speeds. I don't know the typical axon lengths (please tell me if you know or can refer me to measured distributions of axon length), but this maximum of about 1000mm implies 125 days (8mm/day) or 2.5 days (400mm/day). If we assume the dimension of the brain as a typical axon length i.e. 10cm = 100mm then this becomes 12.5 days (400mm/day) and 0.25 days or six hours (8mm/day). For 1cm we have 30 hours (8mm/d) and 36 minutes (400mm/d). For 1cm to 10cm typical axon lengths and shorter indeed seem like the kind of time frame of learning, i.e. the weights may be modified during sleep, and the delay line of materials undergoing axonal transport in each axon contain echoes or memories of synaptic activity during the day.
You are only coming through in waves
Nice Scissor Sisters reference :-)
I am not familiar with scissors sisters but I know that line from Pink Floyd.
They did a cover of the same song. Worth a listen, it's completely different.
You monster!
There are some staunch Pink Floyd fans on HN today.