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Mind

“Clock-like” Neurons Discovered At Last?

NeuroskepticBy NeuroskepticAugust 4, 2019 8:55 AM

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The brain is buzzing with gamma oscillations – cycles of neuronal activity with a frequency (around 40-60 Hz) higher than that of other major brain waves.

A longstanding hypothesis is that gamma serves as a kind of ‘clock signal’ that enables the coordination and integration of signals. Gamma has even been proposed as the mechanism by which the brain ‘binds’ information from different brain areas into a unitary consciousness.

However, while the gamma-clock hypothesis is intriguing, direct evidence for it has proved elusive. Many researchers now believe that gamma is merely a non-specific marker of neuronal activity.

Now, in a new paper out in Neuron, researchers Hyeyoung Shin and Christopher I. Moore announce the discovery of a new class of neurons that seem to have clock-like properties, and firing regularly at gamma frequencies. This could help to put the gamma-as-clock theory back on the map.

Using single-cell tetrode recordings from the cortex of mice, Shin and Moore discovered a subset of fast-spiking interneurons that show highly regular firing in the gamma frequency range.

What’s more, these highly regular interneurons did not show any response to sensory stimulation (whisker touching). This supports the idea that they might have a clock-like role, because the purpose of a clock is to provide a consistent signal independent of whatever else is happening.

So Shin and Moore named their discovery with the catchy title of gamma-regular non-sensory Fast Spiking (grnsFS) cells.

Histogram of firing rates
Histogram of firing rates (inter-spike interval, ISI) of individual fast-spiking interneurons in mouse barrel cortex. In green, the subpopulation of “gamma-regular” neurons is seen to fire every 20-30 ms, i.e. 33-50 Hz. From Shin & Moore (2019) Neuron

Yet if grnsFS neurons are firing away regardless of sensory input, why is it that many previous studies have shown that gamma amplitude and frequency does vary with stimulation? The strong sensory influence on gamma has in fact been one of the pieces of evidence against gamma-as-clock.

Shin and Moore resolve this dilemma by showing that grnsFS cell firing isn’t correlated with the local field potential (LFP), which is a measure of the firing of many neurons, rather than single cells.

If grnsFS gamma firing isn’t reflected in the LFP, this suggests that previous studies using LFP might have completely overlooked the role of grnsFSs. If this is true of LFPs, I suspect it would also apply to EEG and MEG recordings, which are most commonly used in humans.

In my view, this is a convincing study and it should serve to rekindle interest in gamma, which in recent years has come to be seen as a marker of neural activity but not an interesting phenomeon in its own right.

However, Shin and Moore don’t directly show that grnsFS cells are important in perception or coordinating behavior.

The authors show correlations between grnsFS firing and mouse behaviour (i.e. whether the mouse noticed the whisker stimulation), but the crucial experiment for the future would be to somehow inhibit grnsFS cells and show that this disrupts perception. Until this is done, it remains possible that the grnsFS cells are themselves just some kind of marker of neural activity elsewhere.

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