Understanding the brain through controlling it

By Grant Jacobs 06/11/2010

Weekend video (for non-specialists).

In the TED lecture below, Gero Miesenböck presents his work in optogenetics, examining the function of the brain through creating animals where specific neurons (nerve cells) are made sensitive to light.

He has a very dry sense of humour dropped in places of his lecture.

The talks towards the end touches on the physical nature of intelligence and decision making.

Before watching the video, readers may find it helpful to read what I have written below the video to try explain a little of the science. His lecture is very good, but for some a more ‘physical’ description might help.

About 6 minutes into his lecture he refers to pores or channels used to controlled electrical currents in neurons (nerve cells). These channel proteins are the key element of his work. These are similar to the channel proteins I briefly introduced that are defective in the kittens with myotonia congentia.

A transgene is a gene inserted into a species’ genome from another species. Blue-green algae have gene for channel proteins that respond to light. The proteins encoded by this gene are used by these algae to move towards light (phototaxis).

Neurons work, in part, by controlling ions moving in and out of the neuron. The movement of ions is controlled by channel proteins. (The kittens have a defective anion channel protein that in their case affects their skeletal muscles. Readers may wish to read that article for more on ion channel proteins; I’m not going to repeat it here! (Start from ‘Cells are enclosed in membranes…’))

The researchers inserted transgenes containing the algal channel genes (or related genes) into genomes of insects (fruit flies). In the insects where the algae transgene is only active in some neurons (nerve cells), researchers can control those neurons by light. (More specifically, light at particular wavelengths that the light-sensitive channel proteins encoded by the genes respond to.)

In the presence of the light, these channel proteins will allow ions to pass through them. Without the light, they won’t. The concentration of ions affects the function of neurons the channel proteins are in. Thus, the light can affect the function of the neuron. Hence you can use light to study neuronal function, as a tool to explore how a brain works.

Those wanting further reading can try Miko’s blog article, Putting the genetics in optogeneticswho is picking a Nobel Prize to be awarded in recognition of work in this area – Gero Miesenböck’s review article in Science on optogenetics, The Optogenetic Catechism (2009), or Baier and Scott’s review article on optogenetics applied to Zebrafish, Genetic and Optical Targeting of Neural Circuits and Behavior — Zebrafish in the Spotlight (2009). (Both articles are open-acess according to PubMed, but in practice I can’t access Miesenböck’s article without subscriber access.)

(As an aside there is an indirect connection with one of my own research interests, epigenetics. Epigenetics is the form of genetics that controls the three-dimensional structure and packing of genes. Genes that are not used in a particular kind of cell are packed away, genes that are used are opened to be made accessible for use. Transgenes are only active if they are inserted into a region of the genome that is epigenetically open, accessible to be used. These differ in different types of cells, so in principle at least this work might be allied to epigenetic studies at some point. (You can also create transgenes that are insulated from this effect, that work independently of the epigenetic state it is inserted within.))

Other articles on Code for life:

Fainting kittens – feline myotonia congenita?

Thoughts towards a human brain neural connection map

Neurological shorts

Consumer brain-computer interface

Temperature-induced hearing loss

I remember because my DNA was methylated

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