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First Movie of an Entire Brain's Neuronal Activity

timothy posted about 3 months ago | from the may-not-be-suitable-for-children dept.

Medicine 44

KentuckyFC (1144503) writes "One of the goals of neuroscience is to understand how brains process information and generate appropriate behaviour. A technique that is revolutionising this work is optogenetics--the ability to insert genes into neurons that fluoresce when the neuron is active. That works well on the level of single neurons but the density of neurons in a brain is so high that it has been impossible to tell them apart when they fluoresce. Now researchers have solved this problem and proved it by filming the activity in the entire brain of a nematode worm for the first time and making the video available. Their solution comes in two parts. The first is to ensure that the inserted genes only fluoresce in the nuclei of the neurons. This makes it much easier to tell individual neurons in the brain apart. The second is a new techniques that scans the entire volume of the brain at a rate of 80 frames per second, fast enough to register all the neuronal activity within it. The researchers say their new technique should allow bigger brains to be filmed in the near future, opening up the potential to study how various creatures process information and trigger an appropriate response for the first time."

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Mapping the Nematode? (2)

LifesABeach (234436) | about 3 months ago | (#47275167)

So many questions.
Could a complete mapping of the neural network be accomplished?
Would it be possible to artificially trigger a neuron to verify the mapping?

Re:Mapping the Nematode? (3, Interesting)

Rei (128717) | about 3 months ago | (#47276249)

Why wouldn't it be? Light-sensitive proteins are quite well understood.

All of this leads to a really fascinating possibility down the road...

Part 1: Requirements:

1) Genes are inserted into the nucleus of every neuron.
2) Probes which can receive on one or more optical frequencies** and send directionally on other frequencies (which we'll call A, B, and C) are inserted all throughout the target brain.
3) The genes from #1 flash upon synapse**, allowing the probes in #2 to receive the signals
4) The genes from #1 force a synapse when they receive frequency A from a probe.
5) The genes from #1 suppress synapse when they receive frequency B from a probe.
6) The genes from #1 force the cell to commit apoptosis when they receive frequency C from a probe.

Part 2: For each neuron in the brain (conducted in parallel):

1) The neuron's behavior is studied relative to its neighbors in order to learn precisely what factors control its activation levels. This requires a very accurate neural model, and probably requires a lot more more than a simple one-frequency "I'm firing" signal in #2 and #3 of part 1.
2) The neuron is simulated in a computer based on said inputs
3) The neuron is ordered repressed when the simulator doesn't want it fired, and ordered fired when the simulator wants it fired.
4) The system works its way through all of its neighbors that it influences, doing steps #1-3 of this part upon them and putting them under control of the simulation as well.
5) Once a neuron is entirely isolated and can be handled entirely within the simulation, the signal is sent for apoptosis.
6) This pattern continues until the entire brain exists only in the simulation.

And thus you take any living entity and entirely digitize their consciousness, without any single moment defining their transition from the physical world to the digital one, and without "copying" them.

This is a key first step in something I've been thinking about for a long time, and I'm thrilled to see it. I doubt I'll live to see all the steps, or that anyone alive today will. But I'm thrilled to see the first steps taken down this road.

More near-term, one can envision all sorts of incredible properties with an optical communication link set up with cells. For example, imagine that you instrument cells in a cancerous organ with genes that can be instructed individually to force the cell into apoptosis, and which flash on various frequencies corresponding to various cellular activities. You look for cellular activities which correspond to cancerous behavior, and when you see them, you tell that cell to kill itself. You really have something way better than all of that unrealistic "nanomachine medicine" stuff that sci-fi writers have been obsessing over for ages.

Re:Mapping the Nematode? (2, Insightful)

Ferrofluid (2979761) | about 3 months ago | (#47276461)

You look for cellular activities which correspond to cancerous behavior, and when you see them, you tell that cell to kill itself

That's kind of what's already supposed to happen naturally inside the human body. Cells are supposed to kill themselves if they are severely malfunctioned or are likely to become cancerous. However, if enough of these fail-safe mechanisms are damages within a cell, then that cell becomes cancerous. That's why cancer is so difficult to treat, and why your own immune system has difficulty attacking it -- the cancer cells have gone rogue and are no longer "following orders" to kill themselves.

So, if you were able to insert genes into cells, which would allow the cells to kill themselves upon activation by a certain light wavelength, then what would happen? Say you illuminate the tumour with that particular wavelength. Perhaps 99.9% of the cells will undergo apoptosis, as instructed. But maybe 0.1% acquired a mutation which disabled your fail-safe genes. Now what? Congratulations -- the cancer has now evolved to be resistant to your light-induced apoptosis commands. And you're back to square one.

Re:Mapping the Nematode? (1)

Rei (128717) | about 3 months ago | (#47276843)

But maybe 0.1% acquired a mutation which disabled your fail-safe genes. Now what? Congratulations -- the cancer has now evolved to be resistant to your light-induced apoptosis commands. And you're back to square one.

Cancerous cells still have lysosomes and there's always going to be some way to open them. Cancer cells often have defective lysosome membranes that don't activate under normal circumstances, but they're still there, and still full of enzymes to break down the cell. So long as they're there, there's going to be a way to open them up. Or, forget the lysosomes and just pump out enzymes directly into the cytoplasm. It's not actually that hard to kill a cell. The hard part is always killing only the right cells. The key thing with this is, it's basically implanting data-collecting sensors into each cell, so you know for sure exactly which cells are running awry.

Buthey, let's just assume your scenario is right. Let's say you "only" can wipe out 99.9% of cancerous cells with no side effects. Why wouldn't that alone be regarded as an utterly miraculous treatment in its own right? You're not "back to square one", you've just done 99.9% of the job of killing the cancer, pretty much any other anti-cancer method will finish the job for you.

Re:Mapping the Nematode? (1)

lexman098 (1983842) | about 3 months ago | (#47277875)

You're not "back to square one", you've just done 99.9% of the job of killing the cancer, pretty much any other anti-cancer method will finish the job for you.

It's possible that at some point before a tumor developed there were 99.9% of cells that should have killed themselves actually doing so. The .1% multiplied into a tumor because there was nothing stopping it. The guy that replied to you was making the point that nature has already created multiple (I think 7 or so) mechanisms to get cells to kill themselves and eventually they all fail one by one due to mutation. Your expensive "inject every cell nucleus" method might fail just the same.

That's not to say it isn't worth pursuing. It could be very effective, but just remember all the other ways nature has already tried to do what you're doing before you get too excited

Re:Mapping the Nematode? (0)

Anonymous Coward | about 3 months ago | (#47278427)

All cancer cells to date have been aneuploid. This seems to be important but it is ignored because Peter Duesberg is a proponent of studying it.

Re:Mapping the Nematode? (1)

Jason Goatcher (3498937) | about 3 months ago | (#47278661)

And you're back to square one.

Returning to square one usually means slowing down the cancer, which is pretty awesome in and of itself, especially if you're the one with the cancer.

Re:Mapping the Nematode? (1)

Tablizer (95088) | about 3 months ago | (#47278123)

Would it be possible to artificially trigger a neuron to verify the mapping?

An actual worm doing the Macarena deserves a +5

Re:Mapping the Nematode? (1)

teslar (706653) | about 3 months ago | (#47280213)

Could a complete mapping of the neural network be accomplished?

The C elegans brain has been completely mapped in terms of connectivity a long time ago. See for instance:
http://www.wormatlas.org/neuro... [wormatlas.org]

Would it be possible to artificially trigger a neuron to verify the mapping?

Interesting thought - I'm not aware of anyone having done that but it's been a while since I followed the C elegans literature closely.

C elegans is pressurised, so you can't easily stick an electrode (assuming you had one small enough) next to your neuron of choice to stimulate it. Maybe you could make a secific neuron become light-sensistive and use optical stimulation (the worm's transparent, so that helps) but again, not sure anyone has ever attempted that in C elegans.

The converse has been done repeatedly though: either ablate a neuron using a laser or design a mutant that won't have it in the first place (remember that the C elegans genome is completely mapped too) and see how it affects behaviour.

80 frames/second (4, Interesting)

i kan reed (749298) | about 3 months ago | (#47275203)

If that captures everything, that's the interesting part to me(though I'm sure it's been known to actual neurologists forever). That means the "clock speed" of the human brain is really really really really low, more or less, right? Like our consciousness is pretty much exclusively the result of massive parallelism?

Re:80 frames/second (0)

Anonymous Coward | about 3 months ago | (#47275279)

Interesting that the frame rate roughly ties in with human visual and audio frame rate perception (as used in most video and audio codecs)

Re:80 frames/second (1)

Anonymous Coward | about 3 months ago | (#47275287)

Human neurons fire around 200 times per second (max). I'm not sure about nematodes, but it's probably more than 80. I'm guessing that "captures everything" means "every neuron," not "every time a neuron fires."

But you're right when you say that massive parallelism is a core strength of the brain.

Re:80 frames/second (0)

Anonymous Coward | about 3 months ago | (#47275311)

The rate one piston in a car engine moves is not related to the total output.

Re:80 frames/second (0)

Anonymous Coward | about 3 months ago | (#47275313)

That means the "clock speed" of the nematode brain is really really really really low

FTFY.

Re:80 frames/second (2)

i kan reed (749298) | about 3 months ago | (#47275329)

Sure, okay. There's more than a little evolutionary separation since then. Do you think there's a good reason to assume the difference is dramatic?

Re:80 frames/second (1)

TangoMargarine (1617195) | about 3 months ago | (#47276627)

Yes. #drasticunderstatement

Re:80 frames/second (0)

Anonymous Coward | about 3 months ago | (#47275511)

Which is nothing compared to the clock speed of the hypnotoad!

https://www.youtube.com/watch?v=64Qq31ucGy0

Analog. not digital. (2)

bussdriver (620565) | about 3 months ago | (#47275531)

There is no clock speed. It is asynchronous and analog. Even if it had some kind of natural timing to it, some things will fire faster others slower. Chained signals will have delays along the path. The result is something without any clock speed with operations happening at the speed of analog (as fine grained as the physics allows... so in other words, crazy fast to capture it all in digital.)

Absolute precision will not be required just as analog audio doesn't need to be converted at the rate the individual molecules move and as they differ -- that level of detail is "noise" even if it is not actual random noise. You can get plenty good approximations with a decent sampling rate... but for this kind of stuff I doubt it's even 200Hz let alone 80Hz. The degree of the signal sent by neurons is not binary... so if you were thinking maybe it's 8bits... somehow I can't see how creatures which can hear better than 8bit 11 Khz audio would think at a slower rate. (ok i realize the ear is physically doing the FFT so the brain only gets the spectrum.)

Re:Analog. not digital. (2)

dinfinity (2300094) | about 3 months ago | (#47277869)

Well, there's no central clock speed, but there are definitely clear instances of macroscopic synchronous behaviour in the brain:
http://en.wikipedia.org/wiki/N... [wikipedia.org]

Re:80 frames/second (1)

Nyder (754090) | about 3 months ago | (#47275595)

If that captures everything, that's the interesting part to me(though I'm sure it's been known to actual neurologists forever). That means the "clock speed" of the human brain is really really really really low, more or less, right? Like our consciousness is pretty much exclusively the result of massive parallelism?

If you bothered to read the summary, you'd see it was a nematode worm brain, not a human brain. 80 fps was good enough for that worm's brain. Most likely not good enough for a human brain. but possibly good enough for bigger animal brains.

Re:80 frames/second (1)

i kan reed (749298) | about 3 months ago | (#47275681)

I did read the summary. I get that there are differences.

100 step rule (2)

NotInHere (3654617) | about 3 months ago | (#47277631)

Its amazing [teco.edu] :

For example a human can recognize the picture of another person in about 100 ms. Given the processing time of 1 ms for an individual neuron this implies that a certain number of neurons, but less than 100, are involved in serial; whereas the complexity of the task is evidence for a parallel processing, because a difficult recognition task can not be performed by such a small number of neurons, example taken from [zell94, p24,]. This phenomenon is known as the 100-step-rule.

Where's the Video? (0)

Anonymous Coward | about 3 months ago | (#47275265)

Maybe I'm just blind.... but I couldn't find the video anywhere in the article. But the link says they've made it available. Is there a link?

And (1)

nani popoki (594111) | about 3 months ago | (#47275275)

Siskel gave it two thumbs down.

Re:And (0)

Anonymous Coward | about 3 months ago | (#47275867)

Amazing, since he's dead

Ever So Much Closer... (1)

0xG (712423) | about 3 months ago | (#47275285)

...to understanding women!

Having no idea... (2)

NMBob (772954) | about 3 months ago | (#47275379)

Do neurons just fire or not fire in a binary fashion, or are there different levels/voltages of on and off?

Re:Having no idea... (2)

raftpeople (844215) | about 3 months ago | (#47275573)

Short answer: yes, different levels.

Longer answer: There is much complexity and the real answer would probably cover a few books. But a few highlights: neurons have their firing rate and their spike levels modulated by a variety of things in the brain. Glial cells (which are 10x more numerous than neurons) inhibit and disinhibit neurons, communicate with each other and are involved in computation. Some neuron communicate with a continuous flow of protons (inner ear, acceleration detection), some fire locally on their dendrite instead of the typical method of sending a signal down the axon. There have also been recent discoveries linking microtubule quantum vibrations to anesthesia effects (implying it is part of computation).

Re:Having no idea... (1)

NMBob (772954) | about 3 months ago | (#47275725)

We're going to need a computer to figure that all out. :) Thanks for the info. I guess I'd better go find something to read on the subject. It all, literally, boggles the mind. Did that nematodes brain actually only have a couple/few dozen neurons?

Re:Having no idea... (1)

NMBob (772954) | about 3 months ago | (#47275759)

Oops...read the article. 302 neurons. They were not looking at all of them.

Re:Having no idea... (1)

raftpeople (844215) | about 3 months ago | (#47277001)

That worm brain is well studied, but they still do not understand how it works. Whenever you see something about someone simulating a human brain, or a cat brain, or a rat brain, just remember that the people working on this stuff realize that even 302 neurons are still too many to understand currently.

Re:Having no idea... (1)

LetterRip (30937) | about 3 months ago | (#47278773)

I wouldn't call 20 years ago 'recent'.- Penrose Harmerhoff Orch Orr model was using the data on microtubules and anesthesia as support for the quantum conciousness theory in 1995.

Re:Having no idea... (0)

Anonymous Coward | about 3 months ago | (#47281141)

Before it was an idea, recently there is actual evidence to support the idea.

During the next conference on neuroimaging (0)

Anonymous Coward | about 3 months ago | (#47276141)

"You call that a brain? This is a brain!"

"movie" (0)

TangoMargarine (1617195) | about 3 months ago | (#47276599)

Am I the only one that is annoyed whenever someone uses "movie" as a synonym for "video?" A video has to at least approach an hour long and *have a plot* before it's a movie in my book.

P.S: What the heck is up with websites with huge font sizes these days? It's like getting punched in the face. And after ctrl-scrolling out like 4 notches, the white bars on each side of the text is over twice the size of the text itself.

</curmudgeon>

Remarkable achievement? (1)

t_ban (875088) | about 3 months ago | (#47276679)

The entire brain of a nematode worm??? You don't say!!!

Re:Remarkable achievement? (1)

perceptual.cyclotron (2561509) | about 3 months ago | (#47284975)

Well not quite. But almost 70% of the head ganglia! ... So probably closer to 180 or so neurons total. Colour me impressed in so far as the methodology is concerned – but if anyone thinks these cute little movies are going to help them more than the existing full wiring diagrams and some high quality patch-clamp data, they're delusional. Get me a drosophilia or a mouse and we can talk.

If it were my brain... (1)

trailerparkcassanova (469342) | about 3 months ago | (#47277835)

it would be a one-reeler.

OT: Submitter, where'd you get your username from? (1)

The New Guy 2.0 (3497907) | about 3 months ago | (#47278165)

KentuckyFC, you seem to need a trademark license to use that username... where'd you get that from?

optogenics worseless (1)

strstr (539330) | about 3 months ago | (#47279815)

I read the article and was impressed by the retarded idiocy of the research. What these idiot researchers are doing is making the nerons glow through genetic modification in optogenics in new spectrums. However neurons always glowed prior to modification in lower frequencies when observed with the right technology because neurons full of electrons generate electromagnetic frequencies and neurons can be observed as on or off known as evokes potentials.

Using a radar machine in the military or a technique called electron spin resonance one can illuminate the brain with radar, or frequencies between 1MHz and 100THz and map out unpaired electrons thus whole brain electrical activity. Once this is done full EEG maps of the brain can be created and active an inactive neurons distinguished through electron mapping. The military has had this technology since 1974.

What's more is we can monitor individual synapses with this technology or individual parts of atomic structure not just whole neurons. It's fully patented by Robert Malech a DOD contractor too (1974).

I am not joking. This whole system is entirely classified because the government uses it to warrantless spy on and covertly hack and attack people. More details at including the radar patent http://www.obamasweapon.com/ [obamasweapon.com]

Dr. Robert Duncan is a DoD and CIA and US DOJ whistleblower / surveillance architect who likes to leak details about it. Info on the above site including full interviews and his books .

HAARP machinea and satellites remain the most advanced radar on earth above what any researcher is using in the public. Essentially MRI etc are toys compared to what the government has tucked away and pointed at us in secret.... XD

corrections (1)

rackeer (1607869) | about 3 months ago | (#47279967)

They record calcium activity in neurons. Calcium is a marker of neuronal activity (although the dynamics are slower than electrical ones). Calcium recording in the nematode is difficult, because the neurons are small, and the spread of calcium is very broad. The method is impressive and a great breakthrough. However...

1. A brain is a center of the nervous system. It's not strictly correct to speak of brains of nematodes. They don't have this separation of their nervous system. In the article they write of the anterior nervous system of the nematode, and say that their technique could be applied to brains of other animals. 2. The short clip is not a recording of all neurons. It's 70% of the neurons contained in the head ganglia.

Some people here speak of the mapping of the network. This was already done in 1986. The nematode is highly stereotypic. It's known what neurons there are (they all have acronyms), how many, and what they are connected to. The weight of these connections is not clear yet however. What is not clear are the associated neurotransmitters to these synapses and the strength of synapses. This determines how strongly neurons modulate each other and if the modulation is excitatory or inhibitory.

With some caveats in place, the potential of the recordings based on this technique is to help to get to the connection strengths, and to a functional connection diagram that then can potentially be used for predicting the animals behavior.

"First movie," srsly? (1)

mick129 (126225) | about 3 months ago | (#47379067)

Neuroscience is a whole field dedicated to learning how the brain works. Do you really think that there has never been a video made of whole-brain neuronal activity? Ever heard of fMRI [wikipedia.org] ? That's the most common way to track activity over time, which - guess what - makes a video. There are many other imaging modalities which can be used to measure activity over time.

It's the first time this method was used to make a whole-brain record of activity. And it's cute that it uses visible light instead of magnetism or radioactive decay, but that certainly doesn't make it the only video.
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