Neuroscientists have identified brain cells that create various coordinate systems to inform us of our position during a series of behaviors. These cells can execute different action sequences, similar to how a music box can be arranged to produce various melodies. This research enhances our comprehension of the brain’s algorithms that enable it to fluidly generate complex behaviors, including planning and reasoning, and it could shed light on how these processes may malfunction in psychiatric disorders such as schizophrenia.
The study, published today in Nature, details the work of researchers from the Sainsbury Wellcome Centre at UCL and the University of Oxford as they observed mice learning different behavioral sequences that shared the same underlying structure. This approach allowed the team to explore how mice apply structures to new tasks, a key indicator of intelligent behavior.
“Daily, we tackle new problems by drawing upon our existing knowledge. For example, when confronted with a new recipe, you can utilize your understanding of similar dishes to determine the necessary steps, even if you’ve never attempted the meal before. Our goal was to gain a detailed understanding at the cellular level of how the brain accomplishes this and to deduce the algorithms at play as the brain works through these issues,” explained Dr. Mohamady El Gaby, the study’s first author and postdoctoral neuroscientist at the Sainsbury Wellcome Centre and the Nuffield Department of Clinical Neurosciences at the University of Oxford.
The researchers challenged mice with a sequence of four target locations. Although the specifics of the sequences varied, their overall structure remained consistent as the mice navigated through the locations (A, B, C, and D) in a repetitive loop.
“After experiencing numerous sequences, the mice displayed an astonishing ability—they predicted a part of the sequence they had never encountered before. When they arrived at D in a new setting for the first time, they instinctively returned to A. This action couldn’t have been remembered since it had never been experienced before! It indicates that the mice grasp the general structure of the task and can keep track of their ‘position’ within behavioral coordinates,” Dr. El Gaby elaborated.
To delve into how the mice grasped the general structure, the researchers employed silicon probes to monitor the activity of multiple individual cells in a brain region known as the medial frontal cortex. They discovered that these cells collectively tracked the animal’s “goal progression.” For instance, one cell might activate when the animal is 70% toward achieving its goal, regardless of the specific goal or the distance involved.
“Our findings showed that these cells monitored the animal’s behavioral position in relation to tangible actions. Using the cooking analogy again, these cells were concerned with advancements towards subgoals, such as chopping vegetables. A portion of the cells was also attuned to track the progress toward the overall goal, like finishing the meal preparation. Hence, these ‘goal progress’ cells essentially function as adaptable building blocks that collectively form a behavioral coordinate system,” stated Dr. El Gaby.
Ultimately, the team discovered that these cells create multiple coordinate systems, each indicating the animal’s position concerning particular actions. Just as a music box can be arranged to produce any series of notes, the brain can similarly “perform” behavioral actions.
The team is currently investigating how these activity patterns integrate into the brain’s networks, both during the learning of new behaviors and as they begin to emerge in the developing brain. Additionally, preliminary research from the group and their collaborators indicates that analogous brain activity appears in similar circuits within healthy humans. This insight has motivated the team to collaborate with psychiatrists to explore how these processes might be disrupted in conditions such as schizophrenia, which is linked to similar brain circuits. This could illuminate why individuals with schizophrenia may overestimate their progress toward goals, potentially leading to delusions.
This study received support from several sources, including a Wellcome Trust PhD studentship (220047/Z/19/Z), a Wellcome Principal Research Fellowship (219525/Z/19/Z), a Wellcome Collaborator award (214314/Z/18/Z), core funding from The Wellcome Centre for Integrative Neuroimaging and The Wellcome Centre for Human Neuroimaging (203139/Z/16/Z, 203147/Z/16/Z), the Sir Henry Wellcome Post-doctoral Fellowship (222817/Z/21/Z), the Gatsby Charitable Foundation, the Wellcome Trust career development award (225926/Z/22/Z), and a Wellcome Trust SRF (202831/Z/16/Z).
