It all started with ketamine. To some, vets mainly, it’s a horse tranquilliser. To others, a party drug. To those with severe clinical depression, a potential, literal, life-saver. A dose of ketamine can rapidly dull the symptoms of depression, providing immediate relief for those crippled by the darkest thoughts. And while ketamine does not work for everyone, it seems to work in many people who are untouched by standard anti-depressant drugs.
Ketamine could then be our best lead in the hunt for depression. For if we search for where ketamine affects the brain, and for how it affects the brain, we will get vital clues to the cause of depression. And so to a long-lasting effective treatment. Two studies just published in Nature used precisely this trick, and spectacularly uncovered not just compelling evidence of the tiny brain region to target, but exactly what goes wrong in it to create depression — that some neurons are, literally, depressed.
The hunt for depression is a tricky case for any neural detective. Your brain has 86 billion neurons. Where to start looking for suspects? Well, let’s think about that for a second. We want somewhere in the brain that can control how you feel things are going — that things are sometimes better than expected, and worth enjoying. And somewhere in the brain that has something to do with serotonin, because the long-standing treatment for clinical depression are “SSRIs”, drugs that make more serotonin available by stopping it from being mopped up.
Enter the lateral habenula. Rolls off the tongue, doesn’t it? But it fits the suspect’s profile. It connects to both serotonin and dopamine releasing neurons. When dopamine neurons burst with activity, that’s a signal we just got something better than expected (serotonin neurons might signal a similar thing). And when the lateral habenula releases a burst of activity, it stops the dopamine and serotonin neurons from bursting. Stops them from telling the brain — hey, that was unexpected.
