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being flexible And learning to adapt when the world changes is something you practice every single day.
Whether you’re faced with a new construction site and have to redirect your commute, or you’ve downloaded a new streaming app and have to relearn how to find your favorite show, changing familiar behaviors in response to new situations is an essential skill.
To make these adjustments, your brain alters its activity patterns within a structure called the prefrontal cortex—a region of the brain brain Critical for cognitive functions such as attention, planning and decision making. But what specific circuits “tell” the prefrontal cortex to update its activity patterns in order to change behavior is unknown.
We are a team of neuroscientists who study how the brain processes information and what happens when this function is disrupted.
In our newly published research, we have discovered a special class of neurons in the prefrontal cortex that may enable flexible behavior and, when disrupted, may lead to conditions such as schizophrenia and bipolar disorder.
Inhibitory neurons learn new rules Inhibitory neurons inhibit the activity of other neurons in the brain.
Researchers have traditionally assumed that they only send their electrical and chemical outputs to nearby neurons. However, we found a specific class of inhibitory neurons in the prefrontal cortex that communicate over long distances with neurons in the opposite hemisphere of the brain.
We wondered whether these long-term inhibitory connections are involved in coordinating changes in activity patterns across the left and right prefrontal cortex.
By doing so, they may provide the crucial signals that help you change your behavior at the right time.
Researchers have traditionally assumed that they only send their electrical and chemical outputs to nearby neurons. (source Getty Images)
To test the function of these long-term inhibitory connections, we observed rats perform a task that required them to learn a rule to receive a reward and then subsequently adapt to a new rule in order to continue receiving the reward.
In this task, mice dig through bowls to find hidden food. At first, the smell of garlic or the presence of sand inside a pot may indicate the location of the stash food. The specific cue associated with the reward would change later, forcing the rats to learn a new rule.
We found that silencing the long-term inhibitory connections between the right and left prefrontal cortex caused the rats to get stuck or persevere in one rule and prevented them from learning new ones.
They couldn’t change gears and learned that the old signal was now meaningless and the new signal was for food.
Brain waves and flexible behavior
We also made surprising discoveries about how these long-term inhibitory connections create behavioral plasticity. Specifically, they synchronize a set of “brain waves” called gamma vibrations across the two hemispheres.
Gamma oscillations are rhythmic fluctuations in brain activity that occur about 40 times per second. These fluctuations can be detected during many cognitive functions, such as performing a task that requires holding information in your memory or making different movements based on what you see on a computer screen.
Although scientists have observed the existence of gamma oscillations for several decades, their function has been controversial.
Many researchers believe that synchronizing these circadian fluctuations across different brain regions serves no useful purpose. Others have speculated that synchronization across different brain regions enhances communication between those regions.
We found a very different potential role for gamma synchronization. When long-range inhibitory connections synchronize gamma oscillations across the left and right prefrontal cortex, it also appears to be the gateway to communication between them.
When the rats learn to ignore a previously established rule that no longer triggers a reward, these connections synchronize the gamma oscillations and seem to prevent one hemisphere from maintaining unnecessary patterns of activity in the other.
In other words, long-range inhibitory connections seem to prevent inputs from one hemisphere from “getting in the way” of the other half when it’s trying to learn something new.
For example, the left prefrontal cortex can “remind” the right prefrontal cortex of the usual course of action. But when long-term inhibitory connections synchronize these two regions, it also seems to shut down these reminders and enable new patterns of brain activity that correspond to your new commute.
Finally, these long-term inhibitory connections also lead to long-lasting effects. Turning off these connections just once caused the mice to have difficulty learning new rules after several days.
Conversely, rhythmically stimulating these connections to synchronize gamma oscillations artificially could reverse these deficiencies and restore normal learning.
Cognitive flexibility and schizophrenia Long-term inhibitory connections play an important role in cognitive flexibility. The inability to adequately update previously learned rules is one of the hallmarks of cognitive impairment in psychiatric conditions such as schizophrenia and bipolar disorder.
The research also noted deficiencies in gamma synchronization and abnormalities in a class of prefrontal inhibitory neurons, which includes the ones we studied, in people with schizophrenia.
In this context, our study suggests that therapies targeting these long-term inhibitory connections may help improve cognition in people with schizophrenia by synchronizing gamma oscillations.
Many details about how these connections affect brain Circles remain unknown. For example, we don’t know exactly which cells within the prefrontal cortex receive input from these long-term inhibitory connections and alter their activity patterns to learn new rules.
Nor do we know whether specific molecular pathways produce long-lasting changes in neural activity.
Answering these questions could reveal how flexibly the brain shifts between maintaining and updating old information, and potentially lead to new treatments for schizophrenia and other psychiatric conditions.
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