Of all the stuff I came to do as a neuroscience undegrad there is one thing I particularly like to brag about. I shone lasers into mice brains, sliced them (brain, not mice) and created pretty fluorescent pictures out of them. Isn’t this the coolest opener at a party?
The way to have this kind of fun is called optogenetics and it is one of the hottest techniques in neuroscience right now. Pioneered by Karl Deisseroth of the Stanford University, this method is spreading like a wildfire through the neuroscience world and that for a good reason. As the name already suggests, genetical and optical technology are at play there. Gene technology is used to make specific cells light-sensitive, that is, to make them activate (or to shut down) when light falls on them and optical methods (=light) are used to subsequently manipulate these cells. This is done by the following steps:
- taking a gene encoding a light-sensitive protein from a fluorescent pond algae,
- spicing it up with what is called a specific promoter which acts like a password and ensures that the gene only gets expressed in the specific cells of interest,
- inserting this biochemical cocktail into a carriage virus (viruses have evolved to carry genetic information in them and then replicating it in the host cell),
- injecting it into the rodent’s brain and implanting a light delivery mechanism — optical fibre— in it’s skull,
- waiting for a couple of weeks to let the gene express and then finally shining a light onto the manipulated cells in order to turn them on or off.
Can you already guess what it means for the research? It means PLENTY (I will try not to fangirl too hard). We can overcome the caveats of previous methods such as electrophysiology (spatial precision not optimal, meaning you can accidentally coactivate cells you don’t intend to bother) or pharmacological manipulations (drugs’ effects are too slow compared to the real-life neurotransmission). We can achieve unprecedented specificity — we can manipulate specific ion channels or cells secreting a specific neurotransmitter, we can go very deep in the brain and reversibly activate a particular subset of neurons, we can perform manipulations at the real working speed of the brain, we can establish causal relationships between phenomena which were previously solely correlated, for God’s sake!
TL;DR: It is now possible to basically switch a behaviour associated with a specific neuronal circuits on and off again on a milliseconds time-range in living and freely moving animals. I hope you are as excited as me by this point. If not, hold on, it will get even better (spoiler: some videos are coming).
So far it sounded pretty theoretical, so let’s look at some spectacular examples.
1) Amygdala is an almond-shaped structure deep in your brain playing role in things like emotional processing, fear conditioning and aggressive behaviour. Researchers managed to dissect its neuronal circuitry, identifiying two non-overlapping subpopulations of its medial part and showed how they are responsible for different social (e.g. aggression) and asocial (e.g. repetitive self-grooming) behaviours. Moreover, the subpopulations act in an antagonistic manner meaning that when one is active, another one is suppressed. Let’s see how it worked. When researchers artificially activated inhibitory neuronal subpopulation in the medial amygdala this happened (I couldn’t insert the videos over legal issues so click on the link, scroll ALL THE WAY DOWN to “Supplementary information” and click on the Video 1. Believe me, it’s worth the effort):
The mouse went from Dora the explorer to a blood-thirsty viking!
Whereas when the second, excitatory, cell subpopulation was activated this happened (now do the same but with Video 3):
The mouse just forgot about protecting it’s territory and went totally hippie and relaxed.
2). Another fascinating example which made rounds in the media is creating a false memory in a mouse. While an MIT scientist Steve Ramirez was listening to Taylor Swift and wishing he could forget about his ex he started to wondering whether it is possible to manipulate memories. The result of these wonderings was astonishing: he and his colleagues made a mouse believe that something terrible happened in an environment where actually nothing bad happened. It went like this: they tagged the cells which encoded the memory for a specific context (a harmless box A) with the light-sensitive proteins and then optically activated this memory in another box simultaneously with a delivery of a foot-shock. This way mouse was made to associate a traumatic experience with a memory of a context not connected to this experience. Indeed, when placed back to the box where nothing happened, the mouse froze in fear, seemingly waiting for the electrical shock to come.
Of course, there are much more studies using optogenetics ranging from changing the valence of memories connected to specific contexts (hello, PTSD treatment!) to reversing acquired blindness. And, of course, it is not the long awaited flawless technique send to us from above. It has its flaws and challenges and we are still far from implementing it in humans. But hey, who would have thought ten years ago that something like that would be possible?