When exploring a new environment, mice use a unique remote connection in the brain that prompts them to pay attention to the environment’s most salient features, according to a new study from UC San Francisco. The connection, which originates in the prefrontal cortex and extends to the hippocampus, provides clues as to how the brain’s higher cognitive regions refine operations taking place in distant brain areas.
“This circuitry is a gateway to understanding how the brain enables the prefrontal cortex to regulate other parts of the brain from the top down,” said Vikaas Sohal, MD, PhD, senior author of the study, published in April 28, 2022 became cell. “It’s a type of long-range inhibitory pathway that connects two brain regions that hasn’t been seen before.”
Sometimes referred to as the “CEO of the brain,” the prefrontal cortex (PFC) controls executive functions such as attention, planning, and decision-making. The hippocampus stores memories and processes spatial information that helps us navigate our surroundings.
The newly discovered circuitry facilitates the ability to focus attention on what’s important in the environment and ignore other sensory stimuli, said study lead author Ruchi Malik, PhD.
It’s like the PFC picks up all this sensory information and says, “Hey, hippocampus, we’re in this specific context, so pay attention to this specific information now.”
Ruchi Malik, lead author of the study, University of California – San Francisco
She cites the example of a parking lot as the context in which the PFC exerts this type of top-down control over the hippocampus. “To remember where you parked, the PFC would tell the hippocampus to selectively pay attention to landmarks and then remember and look for those landmarks when you return,” Malik said.
Fine-tuning attention by inhibiting neurons
What is unique about this circuit is the complex way it performs the task of focusing attention: it increases and focuses activity in specific hippocampal microcircuits by turning off signals that those microcircuits would otherwise suppress. The result is a very clear signal from the PFC telling the hippocampus what to look for, and an extremely clever means of fine-tuning that message as the environment changes.
The team demonstrated this by putting mice in a small arena containing some small objects for 10 minutes. While exploring the arena, the mice inspected the objects for a minute or two and then moved on. Based on the activity in the mice’s brains, the researchers saw that the signals between the two brain regions synchronized.
When a mouse passed this object again, the researchers could see that the signals in the hippocampus were refined and amplified.
“There this dialogue took place; the hippocampus mapped the locations of objects in space, and the PFC educated the hippocampus on the relevance of each location,” Malik said.
The team also found that the data showed which neurons were firing at any given moment and identified where the mouse was at that moment, confirming that brain activity changes as the mouse approaches or examines an object , which the PFC considers important.
This suggests that when the prefrontal cortex detects that the mouse is approaching an important target, such as a new object, the hippocampus is also fine-tuned in mapping the environment to generate specific patterns of neural activity.
Dysfunction of the brain circuitry can be associated with dementia, ADHD
The team wants to get a better sense of what role this circuitry might play in executive function and the consequences of not being able to do its job effectively. Malik believes that dysfunction in this pathway could underlie cognitive problems related to attention or memory, such as: B. dementia, ADHD or psychiatric disorders.
Your next step toward that goal is to get a feel for how this circuit affects behavior by looking at how it works in more complex activities, such as:
Malik thinks it’s likely that this connection from the higher-order cognitive part of the brain to the older and more universal orientation center can have a broad impact.
“To operate in a complex environment, to search for food or rewards and then come back, you have to be able to pay attention to certain stimuli and place them precisely in space,” she said. “The filter work of this circuit is absolutely essential.”
This research was supported by NIMH grants R01MH106507 and R01MH117961.
University of California – San Francisco
Malik, R. et al. (2022) Top-down control of hippocampal signal-to-noise ratio by prefrontal distant inhibition. cell. doi.org/10.1016/j.cell.2022.04.001.