▎ WuXi AppTec content team editor
Whether it's casually uttering a word or helping us taste and chew food, the movement of the tongue in a variety of scenarios exhibits jaw-dropping flexibility and coordination, essential for us to explore everything, communicate, and even survive. Behind these behaviors, the control of neural circuits is naturally indispensable.
Unfortunately, the scientific community currently has limited understanding of the mechanisms that control the complex sequence of motions of the tongue (mouth). Regular mice in the lab also lack a voice on this issue. Mice can't tell us directly what we think, and scientists haven't established behavioral paradigms that characterize their complex motor sequences.
Now, a new study published in the journal Nature has changed that. Professor Daniel H. O'Connor's team at Johns Hopkins University School of Medicine analyzed the key brain regions that control the movement of mouse oral sequences, revealing how neurons in different regions process figurative and abstract sequence information, laying the foundation for more mouse-based research.
Lead author Many PhDs, now postdoctoral fellows at the University of California, San Francisco, said: "This discovery greatly increases the likelihood of future research in mice, and further answers the loops and computer systems of mouse-level integration." ”
The mice involved in the study were able to quickly perform a series of specific actions with their tongues beforehand under the training of the research team. In the dark, the research team trained the mice to lick in turn to different positions in front of them, get tactile feedback after licking the target, and quickly turn to the next target. During training, mice can lick through 7 given positions in 1 sec. And these continuous movements will constitute a set of oral movement sequences.
Under normal circumstances, mice continuously touch the target at a specific location to complete a set of oral movement sequences (video source: Reference[1])
Since it was not clear which brain regions were involved in controlling the mouse's oral sequence movements, the first thing the study had to do was to find the corresponding brain regions. Optogenetics can precisely manipulate the activity of specific brain regions, and using this technique, the research team sequentially inhibited the activity of different brain regions in mice, and then observed the behavior of mice when licking.
The results showed that when the anterior motor cortex (ALM) of the frontal lobe was inhibited, the mice would not be able to turn on the above sequence behavior, or the movement ability of the tongue would decrease, while after inhibiting the primary sensory cortex (S1TJ) of the tongue and jaw, the sequence of movements of the mice would be disrupted, but the motor ability of the mice was not affected.
▲Response of mice when ALM and S1TJ are inhibited, respectively (Video source: Reference[1])
Therefore, with the help of optogenetic techniques, the brain regions involved in controlling the movement of this sequence were identified: ALM, S1TJ and M1TJ. What role do these brain regions each play in this process? The next single-cell resolution electrophysiological record gives the answer.
▲Optogenetic means inhibited different brain regions in mice (Image source: Reference[1])
In these three brain regions, the S1TJ and M1TJ neural clusters encode more real-time movement information about the tongue itself, such as the length and angle of the tongue sticking out at this moment; in contrast, ALM encodes information that is more abstract and has a higher level, such as the target orientation of the task, which sequence is being completed, and how far away from the reward at the end of the sequence. It is this information that organizes the single movement of the tongue into sequences. Subsequent studies have shown that mice can achieve information integration across three levels: individual actions, sub-sequences, and total sequences.
In order to test whether the sequence of the society is unchanged and can be adjusted according to changes in external conditions, the research team carried out the next experiment. They changed the expected sequence halfway through the experiment, and the mice quickly discovered the changes on their own and responded to them in two different ways.
When external conditions change, the brain needs a "signal bomb" to tell itself that the original sequence should be readjusted. "The signal we detected in the ALM neuron cluster does not encode a concrete action, but rather abstractly expresses the need to abort a current sequence of actions and move to a new sequence," many PhDs said. It is a great inspiration for how the brain monitors biases, inductes errors, and mobilizes sequence branches. ”
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