Auto-Tune, or De-Tune, Keeps the Brain Humming

A more granular investigation into the control of brain waves in setting up transient connections between anatomical locations.

Electrical brain waves (now called neural oscillations) have been a long-standing interest of this blog. They were a relatively early discovery, are tantalizingly dynamic and diverse, but have been resistant to full understanding. But now that understanding is gradually developing, through the relentless process of normal science. A theory put out several years ago laid out in some detail how communcation in the brain can only happen when different locations are in "sync", which is to say that they are firing with the same rhythm, such that the receiving neurons are ready at the right time to process and relay the messages they are getting. But not all areas of the brain can be in sync at the same time, and different areas are positioned at different distances. The model posits dynamic coalitions of co-firing neurons that are in communication at the moment, but which then quickly decay as the thought passes. It also posits that time lags between locations are accounted for in the physiological design, so that for instance, bi-directional communication is not instantaneous, but separated in time such that A-->B happens first, then B-->A happens sequentially, in cases where feedback is an important element. While one of the typical partners of the oscillation entrainment system is stimulus from sensory inputs, another is attention from upper levels, which can emphasize and sustain some coalitions (thoughts) while shunting others to die out.

"Local cortical neuronal groups synchronize by default in the alpha band. During alpha-band synchronization, network excitation fluctuates at 100 ms cycles, but is tracked by network inhibition within 3 ms. This curtails effective communication and renders the respective activity invisible to other neurons. ...Visual scenes induce many local gamma rhythms with varying strength and frequency, reflecting the bottom-up stimulus salience and stimulus history. The gamma landscape in e.g. V1 thus in the end reflects stimulus properties, experience and top-down influences. At a given time point, one out of these coexisting gamma rhythms succeeds in entraining postsynaptic neuronal groups. This gamma entrainment allows to transmit a stimulus representation and to selfishly shut out competing stimuli's representations. The entrainment establishes a cycle-to-cycle memory of the active link that maintains until it is terminated at the end of a theta cycle. The presynaptic gamma rhythm allows network excitation to escape its ever chasing network inhibition." - From a discussion of how the visual processing system may use gamma oscillations (vs other frequencies- alpha, theta) to offer salient results to higher visual areas.

Well, how is all this managed? The core properties of neuronal firing are pretty well understood, particularly that each firing is followed by a brief refractory phase, imposing some of the cyclicity on the system. The anatomy is set in a relatively static way (on this scale) but with connections going in all directions. How can oscillatory entrained coalitions be created in so many different directions? Additional complications and opportunities are introduced by oscillations happening at different frequencies. A recent paper (with review) dives into the particular cells and layers of the hippocampus to lay out one example of how such a system is managed, to a very small degree, by inhibitory neurons.

These researchers are as usual working with mice, and have given up on actual mazes in favor of video mazes so that the mouse's head can be held still. This mouse is running (virtually) through a maze, so is accessing its memories of place and time actively while the researchers get into its head. The image below shows (green) how one of their electrodes pierces the mouse's hippocampus, sampling several layers at once. The neuron of interest (dark red) is gl-B182a, which is an inhibitory (neurogliaform) neuron. Its output is a bit diffuse and slow-acting, compared to the other neurons in the system that are being sampled (the u1 and u2 neurons in the trace shown at bottom. The main trace shows the gamma rhythm, (roughly 75 Hz) whose amplitude rises and falls in time within a slower theta rhythm (bottom, roughly 11 Hz). 

An electrode (green) is stuck through a mouse's brain, in the hippocampus, and records from several cells, including one inhibitory neuron, dubbed gl-B182a. The recording is below, compared to several other traces, such as the incoming gamma rhythm (gray, idealized in black), firing of specific target cells, and an idealized theta rhythm (bottom, black). gl-B182a has a very specific and peculiar firing pattern, right at the trough of gamma waves that are at the high points of the theta rhythm.

They note that the neuron they are following fires around the peaks of the general theta rhythm, and precisely at a trough in the fast gamma rhythm. The whole paper is about how this class of inhibitory neurons is specially tuned to fire with the gamma rhythm, (which is coming in from cortical inputs, through the entorhinal cortex), but is also inhibitory, and has the effect of throwing its target cells (called CA1 pyramidal neurons) off this rhythm again, almost immediately. The interesting thing is that they do not inhibit the firing of their targets overall, but only their timing. Thus the paper claims that they have found a novel class of cells that actively, rapidly, and specifically de-tunes target cells that would otherwise merrily just keep humming along with the incoming rhythm. The point of this is that the cells have already been entrained for a couple of gamma cycles before the effects of this new inhibitory cell kick in, which might be enough to communicate what they have to communicate. So it falls to this inhibitory system to break up the party and reset the local cells so that they can be drawn into new and different coalitions / thoughts.

A model of what is going on above with these inhibitory NGFC cells. The gamma rhythm from elsewhere (teal) comes through the hippocampus and recruits select cells such as the CA1 pyramidal cells (purple). When local synchrony is achieved, the neurogliaform cell (NGFC) steps in with an inhibitory burst, enough to knock them out of rhythm again, without significantly lowering their firing rate.

Granted, this is not a full explanation of what is going on with local information processing or with neural oscillations. Especially, it does not imply that the inhibition is being controlled by higher cortical inputs to these cells that might constitite attention or its opposite, and therefore constitutes some kind of transistor-like gating mechanism. But it is an important ingredient in their usefulness, by modulating how thoroughly local cells get caught up in them. The oscillation keeps on going, but thanks to these inhibtory cells, it is highly selective in which local cells it recruits, and how briefly. Note that since we are talking about the gamma rhythm here, these phenomena go by in a matter of milliseconds, far below our range of awareness. They are thoroughly unconscious, as most of our mental processes are.

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