Thursday, 2 June 2011

The Holographic Brain


According to the holonomic brain theory,
Cognitive function is guided by a matrix of neurological wave interference patterns situated temporally between holographic Gestalt perception and discrete, affective, quantum vectors derived from reward anticipation potentials.
Well, I don't know about that, but a group of neuroscientists have just reported on using holograms as a tool for studying brain function: Three-dimensional holographic photostimulation of the dendritic arbor.

A while ago, scientists worked out how to "cage" interesting compounds, such as neurotransmitters, inside large, inert molecules. Then, by shining laser light of the right wavelength at the cages, it's possible to break them and release what's inside. This is very useful because it allows you to, say, selectively release neurotransmitters in particular places, just by pointing the laser at them.

There's a problem though. The uncaging doesn't happen immediately: the laser has to be pointing at the same point for a certain fixed time. This makes it very difficult to simultaneously stimulate many different points - which is, ideally, what you'd want to do, because in the real brain, everything happens at the same time: a given cell might be receiving input from dozens of others, and sending output to the same number.

One solution is to simply split and block the beam into several smaller, parallell beams. This allows you to hit several spots simultaneously but it suffers from the problem that all the spots have to lie in the same 2D "slice". A bit like how, if you taped several laser pointers together, you could project a complex series of dots onto the wall, but not a 3D one.

This is where holograms come in. As everyone knows, holograms appear to be 3D images. By adopting the same kind of algorithms as are used in the construction of holograms, the authors were able to use a single laser to generate a series of stimulation spots within 3D space. The image above shows that they were able to stimulate a single dendritic spine of a single neuron by uncaging glutamate.

Then they moved on to a real experiment: stimulating several branches of a single cell. What they found was that if you stimulate several branches simultaneously, the overall excitation produced is less than the sum of the individual stimulations.

The bottom graph shows this: the grey line is what you'd expect if it was simply summed. Interestingly, a drug called 4-AP, which is used to provoke epileptic seizures in experimental animals, blocked this effect and made cells respond in a linear fashion.

This is clearly an extremely promising method. I've previously blogged about how it's possible to visualize individual dendritic branches in the living brain using another laser-based method, two-photon microscopy. In theory, therefore, it might be possible to both see, and manipulate, the brain on a microscopic level, all without physically touching it at all.

ResearchBlogging.orgYang S, Papagiakoumou E, Guillon M, de Sars V, Tang CM, & Emiliani V (2011). Three-dimensional holographic photostimulation of the dendritic arbor. Journal of neural engineering, 8 (4) PMID: 21623008

10 comments:

spike said...

OK, so what does it mean that the overall excitation is less than the sum of the individual stimulations?
I bet the results heavily depend on your sample size, region of brain, types of neurons (e.g. NS,BS) and many other factors.
I do admire the technique as well but at the same time think that we have a long way to find answers to those big questions (if there is any!)

Unknown said...

I was digging the abstract until I hit "photolysis of caged glutamate on the dendritic arbor of hippocampal neurons".

Richard said...

Re spike's comment: surely it just implies that dendrites of the neurons under investigation are not simply passive processors of input. I guess the next test is to stimulate the dendrites of different types of neurons with varying levels of excitation/inhibition. This is really important for getting information about how dendrites process input. This method looks pretty good considering how difficult intracellular dendritic stimulation is, and how non-specific (spatially) extracellular stimulation is - though I've yet to read the paper itself :)

Neuroskeptic said...

Meekohi: Damn, you should have read on, you missed the best bit: "the nature of the integration of inputs arriving on multiple dendritic branches". Phwooar.

spike said...

Re Richard: sure, I totally agree with you. My hopeless position here comes from the impression I often get from reading these papers. If you think the authors are trying to say that the brain is more complicated that we think, I'm saying that this is the picture that we all have in our minds for ages and if you think they are trying to describe some of those complicated mechanisms, my answer would be my first comment!
It's a good start though

Unknown said...

Neuroskeptic: Hrmm let's see

photolysis - something plants do?
caged - What you do with pet rabbits?
glutamate - sugary frosting?
dendritic - okay I admit I remember these are the things that stick off neurons
arbor - forest... of dendrites? Fair enough.
hippocampal - some chunk of brain stuff
neurons - those little things in the brain.

I'll give myself a 3/6 on comprehension

In contrast, I pretty much get what "the nature of the integration of inputs arriving on multiple dendritic branches" is saying even if I have no idea what they mean.

Neuroskeptic said...

Meeoki: You've almost got it. "Photo-lysis" means light-induced breaking. Lyse/lysis means breakdown. As in "ana-lysis".

skm said...

This method is so interesting! and I'm going to fall in line behind spoke to say that the implications of the results are also unclear to me.

The linear behavior of mice neurons during stimulated seizures is interesting, but I don't know if it means that sections of the brain in someone who is having seizures would behave similarly.

Looking forward to future blog posts on how people use this method. I bet you can watch how the signals sum before learning something, after learning something, etc.

Pseudonymoniae said...

@spike:

It just means that voltage gated channels are activated along the dendrites which act as additional inputs (although it could partly be due to passive properties, such as current leaking out). Based upon the summary provided here, it looks like this effect was largely mediated by voltage-gated potassium channels (note that 4-AP is a voltage gated K+ channel blocker, which is why it causes seizures) as the measured level of excitation approximately fits the predicted line after it is applied. This isn't new though, we've known for a while that dendrites contain plenty of voltage gated channels--the key point of this paper is to demonstrate the methods.

kozioł said...

Might be quite related (in terms of new ways of looking/manipulating neurons without direct contact):

http://www.ted.com/talks/ed_boyden.html

Remarkable talk, though the end bit is little bit worrying (but exciting at the same time).


p.s. I started reading your blog just recently- and will definetely foolow it regularly, keep it up!