By measuring the fast electrical spikes of individual neurons in the touch region of the brain, neuroscientists have discovered a new type of cell that keeps time so regularly that it may serve as the brain's long-hypothesized clock or metronome.

This type of neuron spikes rhythmically, and in a synchronized manner, independent of external sensations, said the senior author. By "setting the beat," the neurons appear to improve rodents' ability to detect when their whiskers are lightly tapped.

Brain waves with approximately 40 cycles per second -- also known as gamma rhythms -- have been studied since the mid-1930s in humans and rodents, and earlier work from the lab showed that boosting the rodents' natural gamma rhythms helped the rodents detect fainter whisker sensations.

"Gamma rhythms have been a huge topic of debate," the senior author said. "Some greatly respected neuroscientists view gamma rhythms as the magic, unifying clock that align signals across brain areas. There are other equally respected neuroscientists that, colorfully, view gamma rhythms as the exhaust fumes of computation: They show up when the engine is running but they're absolutely not important."

The metronome-like function of the gamma rhythm has been hypothesized before, but has been largely written off because gamma rhythms change in response to sensations, the senior author added. These newly discovered spiking "metronome" neurons -- which spike around 40 cycles a second -- do not.

The findings were published in the journal Neuron.

The authors didn't set out to find metronome neurons, which the researchers call gamma regular nonsensory fast-spiking interneurons. Instead, initially they wanted to study the sensation-driven gamma rhythm.

They used a very precise machine to move whiskers slightly, just at the edge of a rodent's ability to detect movement, while recording neuron activity in the whisker-sensation part of the brain. They wanted to see what was different in the brain when the rodent was able detect the faint tapping of its whiskers compared to when it wasn't.

"We were particularly interested in a subtype of inhibitory interneurons; these cells communicate locally and their main function is to inhibit spikes from other cells," the lead author said. "We found that about one third of these fast-spiking interneurons were 'ticking' very regularly. And ticking more regularly meant that the rodent was better able to perceive subtle sensations."

What made this research distinctive was that the looked looked at the behavior of individual neurons instead of averaged neuron activity. By looking at individual neurons, they found three distinct types.

Some of these neurons spiked independent of whisker sensations and thus would typically have been ignored by scientists -- this group included the subgroup of regularly spiking metronome neurons. The other two subtypes spiked randomly -- some did not change with whisker sensations, and others did. Additionally, they found that the metronome neurons in the touch region of the brain were in synch with one another.

"There's this funny thing where neuroscientists will go into a brain, and once they find a cell that responds to the outside world, they study it," the senior author said. "If it doesn't respond to the outside world, they don't know what to do with it and ignore it. With an electrode in the brain you're hearing this and you're hearing that -- it's very easy to either overinterpret or miss important things entirely because you're not ready to see them."

Human brains also have gamma rhythms, the senior author said. As a next step, the authors want to determine if these metronome neurons exist in primates and humans. They also want to see if metronome neurons exist in other brain regions, as well as determine if specifically enhancing the synchronicity of the metronome neurons using genetic engineering and light impacts rodents' ability to detect faint sensations.

Though metronome neurons are newly discovered, disruptions within the broader group -- fast-spiking interneurons -- have been implicated in a number of neurological disorders including autism, schizophrenia and attention deficit hyperactivity disorder. It is possible that some of these conditions are caused by disturbances of the metronome neuron subtype, but significantly more research is needed to understand how this subtype typically functions, let alone any variations in activity.

https://www.brown.edu/news/2019-07-18/metronome

https://www.cell.com/neuron/fulltext/S0896-6273(19)30564-1