Sprint and then stop? The brain is wired to do math

Summary: The brain naturally implements computational principles and life rules integrated with sensory information to guide movement plans and actions.

A source: Pickover Institute for Learning and Memory

Your new apartment is just a few blocks from the bus stop, but today you’re running late and you see the bus pass you by. You break into a full sprint. Your goal is to get to the bus as fast as possible and then park right in front of the doors (they are never exactly right along the curb) before they close. A new MIT study on mice shows that the mammalian brain is better equipped to implement computational principles to stop quickly and accurately.

It’s as simple as a reflex to stop by yelling at a target after a flat run, but it can be thought of as catching a bus or running to a visually indicated location (like mice) to get a water reward. learned, visible, goal-directed prowess.

In the lab of senior author Mriganka Sur, a professor of neuroscience at MIT’s Pickover Institute for Learning and Memory, such tasks of great interest involve a crucial decision to switch from one behavior (running) to another (stopping). from the cerebral cortex, where the brain integrates the learned rules of life with sensory information to guide plans and actions.

“The target is the entry point to the cortex,” said Sur, a professor in MIT’s Department of Brain and Cognitive Sciences. “Where do I need to stop to reach my goal of catching the bus?”

And here it gets complicated. Mathematical models of behavior developed by Eli Adam, a postdoc and lead author of the study, predicted that the “stop” signal from the M2 region of the cortex, which goes directly to areas in the brainstem that actually control the legs, is processed too slowly.

“You have M2 sending a stop signal, but when you model it and do the math, you see that the signal by itself is not fast enough to stop the animal in time,” Adam said. appears in the magazine Cell Reports.

So how does the brain speed up the process? What Adam, Sur, and co-author Taylor Jones found is that M2 sends a signal to an intermediate region called the subthalamic nucleus (STN), which then sends the two signals down two separate pathways that converge again in the brainstem.

Why? Because the difference in the arrival of those two signals, one after the other, turns from integration, that is, from the relatively slow addition of inputs, to differentiation, which is the direct recognition of change. A count shift will trigger the stop signal faster.

Using engineering systems and control theory, Adam’s model required the necessary speed to stop correctly and differentiation to achieve it, but a series of anatomical studies and experimental manipulations were required to confirm the model’s predictions.

First, Adam confirmed that M2 neural activity increases only when mice stop at a landmark and reach a trained goal. Also, it showed that the STN is sending signals as a result. Other stops did not use this route for other reasons. Furthermore, artificially activating the M2-STN pathway caused the mice to stop, and artificially inhibiting it caused the mice to walk the landmark slightly longer.

Red (“mCherry”) staining highlights motor axonal projections in the M2 cortex. Of particular importance, they are the leader of the subthalamic nucleus (STN). Credit: Eli Adam / MIT Pickover Institute

The STN was obviously supposed to signal to the brainstem, specifically to the pedunculopontine nucleus (PPN) in the mesencephalic motor area. But when the scientists looked at the neural activity that started in M2 and quickly followed in the PPN, they found that different types of cells in the PPN responded at different times. In particular, excitatory cells were active before stopping, and their activity reflected the animal’s speed at stopping.

Then, looking at the STN, they saw two types of activity around the stops—one slightly slower than the other—that were delivered to the PPN either through direct excitation or indirectly through inhibition through the substantia nigra retina (SNr). The net result of the interaction of these signals in the PPN was excitatory inhibition. This sudden change can be quickly found by differentiation to implement termination.

“An inhibitory wave accompanied by inhibited excitement may occur suddenly [change of] signal,” Sur said.

The study, along with other recent papers. Pickover Institute researcher Emery N. Working with Brown, Adam recently produced a new model of how deep brain stimulation in the STN can rapidly correct motor problems caused by Parkinson’s disease. And last year, members of Sur’s lab, including Adam, published a study showing how the cortex overrides the brain’s more deeply embedded reflections in visually guided motor tasks.

Together, such studies can help us understand how the cortex can consciously control instinctually wired motor behavior, as well as how deeper regions such as the STN are important for the rapid execution of goal-directed behavior. A recent review of the laboratory explains this.

Humans hypothesize that the “hyperdirect pathway” of communication from the cortex to the STN may have a broader role than the rapid cessation of movement, extending beyond motor control to other brain functions, such as interruptions and switches in thought or mood.

Funding: The JPB Foundation, the National Institutes of Health, and the Simons Foundation Autism Research Initiative funded the study.

See also

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It’s about movement, math and neuroscience research news

Author: David Orenstein
A source: Pickover Institute for Learning and Memory
The connection: David Orenstein is the Pickover Institute for Learning and Memory
Photo: Photo courtesy of Eli Adam / MIT Pickover Institute

Original research: Open access.
Mriganka Sur et al. “Dynamic control of visually guided movement via cortico-subthalamic projections”. Cell Reports


Dynamic control of visually guided movement by cortico-subthalamic projections

Important moments

  • We developed a visually guided movement task to study the stop signal
  • The M2-STN projection sends a stop signal during visually guided movement stops
  • M2-STN activity bidirectionally controls visually guided movement stops
  • M2-STN pathways for MLR/PPN perform differentiation to control rapid movement

A result

Goal-directed movement requires control signals from higher order regions to regulate spinal mechanisms. The corticosubthalamic pathway offers a shortcut for cortical information to reach motor centers in the brainstem.

We developed a task in which head-fixed mice run to a visual cue, then stop and wait to collect a reward, and investigated the role of midmotor cortex (M2) projections to the subthalamic nucleus (M2) in motor control.

Our behavioral modeling, calcium imaging, and optogenetics manipulation results suggest that the M2-STN pathway can be recruited for rapid and precise control of the pedunculopontine nucleus (PPN) of the mesencephalic motor area via the basal ganglia during visually guided movement.

By capturing physiological dynamics through a feedback control model and analyzing neuronal signals in M2, PPN, and STN, we find that corticosubthalamic projections provide rapid input-output dynamics of PPN activity by differentiating M2 error signal.

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