Research Briefs, Science & Technology

Big discoveries from tiny rodents

In the past decades, the field of neuroscience has made astounding progress toward unravelling the intricacies of the human brain, but much of how it functions remains terra incognita. Adrien Peyrache, a researcher at the Montreal Neurological Institute (MNI) and Canada Research Chair in systems neuroscience, studies how brain structures that control navigation are linked to long-term memory storage, and how sleep plays a role in both of these important functions. 

Peyrache mostly conducts his research on mice. They are surprisingly intelligent creatures with exceptional navigational skills that allow them to maneuver as easily in darkness as in broad daylight. When mice roam around, visual and spatial orientation information is sent to specific neurons deep in the brain known as head-direction (HD) cells. At a population level, these cells function like the needle of a compass: Specific neurons are activated when the head is facing a certain direction. As the mouse turns, other nearby neurons activate, and the compass needle turns. The brain’s navigation system integrates this compass with other inputs, such as the animal’s travelling speed. It then encodes its position in a ‘cognitive map’ located in the mouse’s hippocampus, a region of the brain associated with memory. 

During sleep, the brain does not simply turn off; rather, many regions are surprisingly active.  The movement of a mouse’s brain ‘compass’ during rapid-eye-movement (REM) sleep is almost identical to when it is awake. The ‘needle’ of the compass spins at the same speed as if the mouse were actually roaming freely. 

“It’s like the cortex doesn’t know it’s asleep,” Peyrache said. 

The same structures that are involved in spatial navigation are crucial for consolidating long-term memory, since both involve encoding movement through time and space. How exactly this relationship functions is still unknown, but Peyrache is confident that the data his team have collected so far confirm an important link. His work suggests that, while this phenomenon may occur because inactive neurons quickly die, there could be a link with memory consolidation.

Many complementary methods are used to study mouse brains. One of the main techniques is electrophysiology, which consists of using electrodes to record single neuron firings. Arrays of these electrodes are implanted in the brains of mice, who are then free to roam painlessly while data is collected.

Mice are a useful study subject for many reasons, including the similarity of their brains to other mammals, their small body size, and the vast array of tools that have been developed to study them. Research conducted on rodents can also lead to important human applications. Peyrache has been striving to make this transition in his work for many years, most recently in collaboration with the human electrophysiology unit at the MNI.

“[Our work] is basically bridging the gap between human and animal electrophysiological research,” Peyrache said.

Although electrophysiological technology is quite invasive, there is already a human population set up to further such research. For example, certain patients with epilepsy have electrodes implanted in their brains for clinical purposes, namely to identify the region in their brain responsible for their epileptic episodes. Peyrache compares the human brain to a building to describe how these electrodes work: Electroence (EEG) lets researchers hear a murmur through the walls, intracranial electrodes allow them to listen to conversations through the door, and macroelectrodes let them listen to a single person speaking. If the researchers hear someone speaking nonsense, then they have found the damaged population of neurons.

Peyrache’s work is at the forefront of research regarding single-neuron recording for the brain. Although his planned research on humans is not yet at the stage of ethical approval, it carries great potential. He expounds the virtues of both theoretical and application-driven scientific research.

“Science is not an easy world, but it’s also fantastic and inspiring,” Peyrache said.

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