A nicotine receptor in the brain explains everything

If you are conscious and making sense of the world, you have your dorsolateral prefrontal cortex to thank. Same, if you can remember a string of numbers long enough to walk into the next room and punch them into a telephone keypad. To visualize a goal and then accomplish it -- say, fitting a bulky piece of furniture into your car -- you’re likewise going to need that part of the frontal lobe to be in good working order.

But look under the hood of that marvelous piece of gray matter, as a group of Yale University neuroscientists recently did in “cognitively engaged monkeys,” and you will see the workhorses of the dorsolateral prefrontal cortex. Those are your alpha-7 nicotinic acetylcholine receptors.

For most of us, they’re hard at work all day, but they stand down during deep sleep. In those with schizophrenia or attention deficit and hyperactivity disorder (ADHD), they function poorly. The advance of Alzheimer’s disease appears to silence them almost completely.

As described in an article published Tuesday in the Proceedings of the National Academy of Sciences (PNAS), the alpha-7 nicotinic acetylcholine receptors are situated deep in the dorsolateral prefrontal cortex, where the neurotransmitter glutamate is the principal currency of electrical exchange between synapses. But electron microscopy and recordings showed that not until these specialized receptors are activated can the prefrontal cortex and its working memory circuits come to life.

And dialing up their function in the brains of people with schizophrenia, Alzheimer’s, ADHD or autism may help correct some of those disorders’ symptoms, say the authors of the article in PNAS.

A passel of different agents may work to restore or boost the activity of alpha-7 nicotinic acetylcholine receptors when genetic errors or disease cause them to underperform. One of those is, not surprisingly, nicotine. But researchers are working on a wide range of alpha-7 nicotinic agonists that do not cause cancer when burned and inhaled.

Those could, first and foremost, treat diseases. But they could also someday boost cognitive performance in the healthy.

The central role of the alpha-7 nicotinic acetylcholine receptors actually explains a host of everyday mysteries.

They explain why, when you’re asleep and dreaming, the usual logical constraints of reason just don’t apply. They explain why a jolt of caffeine or a cigarette -- or both -- can dramatically put you back on-task and improve your mood. They explain why people with Alzheimer’s disease quickly lose their ability to project into the future, and why most people with schizophrenia have difficulty conceiving and executing plans. They may even explain why rates of smoking are so much higher among those with schizophrenia: They are medicating themselves, the researchers explain.