A molecular timer that counts out the seconds a thought is held has turned up in the thalamus. Working memory is a mental notepad that keeps information for a few seconds while we read, calculate, or plan. Its capacity is limited, and over time the trace fades. But what exactly sets this time limit remained a mystery for a long time.
The answer came from the thalamus, a subcortical hub that relays signals to the cortex. There, the Gpr12 receptor is at work. Previously, no one knew what activates it, but now it has been figured out: it is anandamide, a lipid from the endocannabinoid family. Anandamide binds to the receptor through an unusual side pocket and triggers a slow suppression of cAMP, an intracellular signaling molecule, in neurons.
This suppression works like an hourglass: it lasts exactly as long as the animal holds information in the task. In mice with increased Gpr12 expression, the suppression persisted at delays of 30 and 60 seconds, while in control mice it disappeared after just 15 seconds. A point mutation in the side pocket canceled both the cAMP suppression and the memory improvement. Administering anandamide to mice improved memory, but had no effect in mice without Gpr12. In macaques, blocking the breakdown of anandamide also improved working memory, and the effect was dose-dependent.
Anandamide got its name from the Sanskrit word "ananda," meaning bliss or joy. It is the same lipid that activates CB1 cannabinoid receptors, but in the thalamus it acts on a completely different receptor, Gpr12, and instead of impairing memory it improves it.
The idea of a molecular timer that counts out the seconds of information retention echoes the concept of the "mental chronometer" from Ted Chiang's "Story of Your Life," where the perception of time and memory plays a key role. More broadly, controlling the duration of working memory resembles the technologies in Philip K. Dick's "We Can Remember It for You Wholesale," except that instead of implants, it is an endogenous lipid.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.