Huge congratulations to @SorayaDunn on her paper in Nature Communications showing behaviourally modulated hippocampal theta oscillations in the ferret persist during both locomotion and immobility. Great to work with her @DanBendor and @jennybizley.
The hippocampus is a brain region that plays an important role in learning, memory and navigation. When you look at the electrical signals within this brain region (known as the local field potential), you see rhythmic activity called oscillations that results from the coordinated firing of groups of neurons. Oscillations can occur at different frequencies, with the strongest being in the theta band. Much like the conductor in an orchestra, these theta oscillations are thought to coordinate communication across thousands or even millions of neurons, both within the hippocampus and between the hippocampus and the cerebral cortex (the folded structure we see on the outside, involved in sensory, motor and many other functions).
Theta oscillations have primarily been studied in rats and mice, where they occur strongly during movement, but diminish when animals are at rest. However, theta is less obvious in other species such as bats, monkeys or even humans, where theta usually occurs only during active investigation of sensory stimuli either using vision (or echolocation in bats). Active sensation is hard to study in rodents, as they’re constantly using their whiskers and sense of smell to explore their environment. It’s therefore unclear if the theta seen in moving rats and mice is related to the fact they’re running around (locomotion), the way they’re collecting sensory information, or fundamental differences in neurobiology between species.
To better understand theta, we need an animal that moves like a rat, but uses its senses more like a human. This is where the ferret comes in! Like us, ferrets have good spatial hearing, and their vision is generally better than rats and mice (though not as good as us). Our question was whether theta in ferrets would be like the rat (widespread and dependent on movement) or like humans (more restricted and associated with sensing). To test this, we recorded theta oscillations in ferrets and rats when animals reported the locations of visual or auditory stimuli. The answer was somewhat stranger than we expected…
In the ferret hippocampus, theta oscillations are everywhere and all the time! Like rats, ferrets show strong theta oscillations during movement, but unlike rats, ferrets also have theta at rest (immobility). Theta at rest might be more comparable to the conditions when such activity is observed in humans during sensory exploration, and it was notable that the theta frequency in ferrets is closer to humans than theta in rats. Theta at rest was observed in multiple different conditions in ferrets, but was strongest during reward periods, when animals successfully reported the location of lights or sounds.
Intriguingly, we could selectively eliminate theta oscillations during immobility using a drug called atropine. Atropine affects the communication between neurons using a specific neurotransmitter called acetyl-choline, which suggests that these brain waves are being generated by a specific sub-system of the brain that uses this chemical to orchestrate activity. Atropine didn’t have any effect on theta during movement, either in ferrets or in rats, supporting the idea that there may be multiple generators of theta at work. You can think of this a bit like the theta rhythm being music played by the hippocampus, but with two conductors swapping in and out to lead the orchestra when playing Mozart or Bach.
Extending this conductor metaphor slightly, the hippocampus of rats and ferrets differ in the conditions under which the conductors change. In the rat, atropine-sensitive theta occurs when animals are exposed to aversive stimuli, like the scent of a predator. In contrast, ferrets (which are themselves predators) show atropine-sensitive theta when rewarded or waiting in anticipation of an important event (the light or sound they’re going to report).
These results show that the way theta oscillations are coordinated in matched behavioral conditions differs between the two species. This is an important step, as most comparisons across species are confounded by different behavioral settings. Moreover, while we expected ferrets to be a link between rodents and humans, given their sensory ecology, it turns out instead that they’re theta extremists! This challenges our understanding of why theta oscillations occur in the hippocampus (more research needed), but also gives us a new, and possibly the best, model in which to study these neurobiological processes.
The implications from this work aren’t just theoretical though… diseases such as Alzheimer’s are known to badly damage the hippocampus, which may explain the declining recall and learning abilities of sufferers. Likewise, oscillatory activity is disrupted in a wide variety of neurological disorders including dementia, where one’s mental coordination deteriorates. To fight these diseases and design effective treatments, we need to understand how the brain actually works, and this requires the fundamental discovery research that we, and many other neuroscientists are trying to drive forward. Hopefully knowing how, and perhaps more importantly why, oscillations are generated in structures like the hippocampus will one day help us rebuild those rhythms artificially in the brains of patients.