Bad stuff would happen if your brain didn’t cycle

"Too much excitation relative to inhibition you get a seizure, too little you become comatose," says Barry Connors. (Credit: Mark Norman Francis/Flickr)

A study with mice shows how the mammalian brain is able to maintain a constant state of up and down—while under anesthesia, during slow-wave sleep, or even amid calm wakefulness.

The findings suggest how the brain walks a healthy line between excitement and inhibition as it strives to be idle but ready, a bit like a car at a stoplight.

“It is very important to regulate that balance of excitation and inhibition,” says Barry Connors, a professor and chair of neuroscience at Brown University and senior author of the study. “Too much excitation relative to inhibition you get a seizure, too little you become comatose.

“So whether you are awake and active and processing information or whether you are in some kind of idling state of the brain, you need to maintain that balance.”

Complicated process

The researchers focused on five different types of cells in a particular area of the mouse cortex and found that all five appear to contribute uniquely to the ups and downs.

Specifically they looked at the activity of excitatory pyramidal cells and four kinds of inhibitory interneurons (PV, SOM, VIP, and NPY) in different layers of the barrel cortex. That part of the cortex is responsible for processing sensations on the face, including the whiskers.

Garrett Neske, a graduate student at Brown University and lead author of the study, induced up and down cycles in slices of tissue from the barrel cortex and recorded each cell type’s electrical properties and behaviors, such as its firing rate and the amounts of excitation and inhibition they received from other neurons.

The picture that emerged is that all types of interneurons were active. This included the most abundant interneuron subtype (the fast-spiking PV cell), and the various more slowly spiking subtypes (SOM, VIP, NPY). In fact, the latter cells were active at levels similar to or higher than neighboring excitatory cells, contributing strong inhibition during the up state.


One way such findings are important is in how they complement recent ones by another research group at Yale University. In that study scientists looked at a different part of the cortex called the entorhinal cortex. There they found that only one inhibitory neuron, PV, seemed to be doing anything in the up state to balance out the excitement of the pyramidal neurons. The other inhibitory neurons stayed virtually silent. In the new study, Neske replicated those results.

Taken together, the studies indicate that even though up and down cycles occur throughout the cortex, they may be regulated differently in different parts.

“It suggests that inhibition plays different roles in persistent activity in these two regions of cortex and it calls for more comparative work to be done among cortical areas,” Neske says. “You can’t just use one cortical region as the model for all inhibitory interneuron function.”

The National Institutes of Health and the Defense Advanced Research Projects Agency supported the research, which was published in the Journal of Neuroscience.

Source: Brown University