Skip to content

Correcting a forebrain signaling imbalance reverses autistic symptoms in mice

A new study, conducted by Stanford psychiatrist, neuroscientist and inventor Karl Deisseroth, MD, PhD, and colleagues and published in Science Translational Medicine, suggests that key features of autism reflect an imbalance in signaling from two kinds of neurons in a portion of the forebrain. The study's findings also suggest that reversing the imbalance could alleviate some of the disorder's hallmark symptoms.

Imagine a computer with a slight tendency to generate more ones and fewer zeroes than it should.

A computer, the human brain is not. Try as we may to get them to fake it, computers haven't the slightest interest in social interactions, much less any emotional reaction (or overreaction) to them.

But our brains do share with their digital analogs -- loosely speaking, anyway -- the use of a binary code for processing information. In a computer, that's done with ones and zeroes. Our brains instead temper pulses of excitation with tugs of inhibition. Well over 90 percent of all the nerve cells (scientists call them "neurons") in our brain are either excitatory or inhibitory, with the rest performing somewhat more nuanced tasks.

With somewhere around 100 billion neurons in the brain, each making on the order of thousands of connections to others near and far, that's a lot of information-processing capacity. We humans, being social animals, need as much of it as we can get.

“Social interaction may be the hardest thing a mammal can do,” Deisseroth told me during an interview for my news release on the study. “It’s an immensely complex phenomenon that requires rapid, highly integrated communication among disparate, distant parts of the brain.”

Around 1 in 80 American children may be coping with autism spectrum disorder, which is characterized by repetitive behaviors and difficulty with (and often extreme anxiety surrounding) social interaction. Scientists have theorized that an excitation-inhibition imbalance might account for these behaviors. Overall healthy brain function, they've hypothesized, requires a delicate balance between excitatory and inhibitory signaling in key brain regions. As I wrote in my release:

One of those regions is the medial prefrontal cortex, which plays a major role in executive functions, such as planning, prediction, attention and integrating information from other individuals’ behaviors and speech for clues as to what they might be thinking.

To test the excitation-inhibition balance hypothesis, the Stanford scientists employed a strain of mice that display classic symptoms of autism. In a series of experiments conducted with this mouse model, the researchers used optogenetics, a high-powered laboratory technology pioneered in Deisseroth's lab, to show that reducing the ratio of excitatory to inhibitory signaling in the mice's medial prefrontal cortex countered these mice's hyperactivity and deficits in social ability.

Because optogenetics requires a form of gene therapy -- the insertion of genes for light-sensitive proteins into specified neuronal circuits, which can then be remotely switched on or off at the flick of a laser-light switch -- don't expect these results to be translated into an off-the-shelf therapy for people anytime soon. But the new thinking about what's causing autism, combined with the pinpoint-precision brain experimentation that optogenetics makes possible, may speed the cure for a disease that, today, has none at all.

Previously: Karl Deisseroth wins 4-million-euro Fresenius Research Prize, Researchers induce social deficits associated with autism, schizophrenia in mice and Nature Methods names optogenetics its "Method of the Year"
Photo by winnifredxoxo

Popular posts

Category:
Genetics
Sex biology redefined: Genes don’t indicate binary sexes

The scenario many of us learned in school is that two X chromosomes make someone female, and an X and a Y chromosome make someone male. These are simplistic ways of thinking about what is scientifically very complex.
Category:
Nutrition
Intermittent fasting: Fad or science-based diet?

Are the health-benefit claims from intermittent fasting backed up by scientific evidence? John Trepanowski, postdoctoral research fellow at the Stanford Prevention Research Center,weighs in.