Lecture 14 - Optogenetics

This week was the 14th and final installment of my graduate Neural Engineering course. This week we discussed Optogenetics - the new breakthrough field that introduces light-sensitive components into cells. These can be used in at least two ways

1. A light-sensitive membrane protein can be added to a cell. When a specific frequency of light is shined on that cell, it will depolarize and fire.
2. By adding light sensitivity to gene promotors, it is/will be possible to up- or down- regulate the production of specific genes under the control a light source.

The genetic material needed to affect these changes is introduced via a standard (or so I'm told) technique called viral transfection in which RNA vectors are placed in a virus (i.e. Lentivirus) which infects cells with the RNA. The cell then uses the foreign RNA to manufacture the desired protein. There are genes which are apparently unique to each individual cell type; by modifying the RNA to only work in conjunction with specific genes, it becomes possible to functionally introduce the desired changes to very specific cell types.

The two papers we read were

• Boyden 2005
• Han 2007

The class was excited about this technique and we worked our way through some of the finer grained technical issues such as how complicated is it to put a fiber optic cable into someone's brain, how large of a light beam would one want (i.e. would you like to turn on one neuron at a time, or entire sections of the brain), and so on.

One interesting question that arose was whether it might be possible to genetically modify the RNA vectors to produce proteins that were sensitive to specific frequencies: i.e. can you program the light sensitivity of a protein? If that were possible, it might be useful to stimulate neurons using wavelengths outside of the visible band, perhaps even radio waves. By using wavelengths of the electromagnetic spectrum that can penetrate the brain, it might be possible to use spatial surface electrodes to target specific brain regions non-invasively.

I'll submit a final report on the class after the student's final projects are due: the first two pages of a grant proposal in which students pitch their idea for the next great neural engineering research project. Students are to submit Specific Aims and Significance sections ala NIH PHS 398 guidelines.