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Mapping delayed responses in the brain

Ecole Polytechnique Fédérale de Lausanne News Jun 23, 2021

Neuroscientists at EPFL identify the brain mechanism that we use to prepare a timely action while suppressing premature execution.

In some ways, we can think of the brain as an input/output machine; it receives signals from the environment and the body through peripheral and sends back appropriate responses. And although this is an oversimplified view of the worlds most complex computer, it is nonetheless the basis of an enormous amount of behavioral research.

For example, a group of researchers led by Professor Carl Petersen at EPFLs School of Life Sciences has published a paper in Neuron where they explore what neuroscientists refer to as a delayed motor response. The importance of the study is self-evident: reacting to stimuli in a timely manner not too early, not too late can be critical, not only for biological, but also social survival.

Our behavior is dominated by internal appetites like want to eat or want to touch, which come up in our mind as we explore the sensory world, says Vahid Esmaeili, one of the studys lead authors. However, it is often critical to wait until appropriate moment before starting an action; for instance, in a sprint race, you get ready with the Get Set signal, but must not move before the Go, regardless of how eager you are.

The researchers explored the mechanism behind delayed motor responses by training mice to perform a behavioral task simulating this process: the mice would first receive a small vibration to their whisker, which acted as a Get Set signal. After a delay, the mice would hear a sound, which acted as a Go signal. If they licked a nozzle soon after Go, the mice would get a drop of sugar water; if they licked it before the sound, they wouldnt. The idea was to train the mice to wait until the Go tone regardless of how eager they were to lick the nozzle after receiving the Get set whisker vibration which predicts the sugar water.

Tracking this delayed response with sophisticated techniques like wide-field calcium imaging, multi-region high-density electrophysiology, and time-resolved optogenetics (activating genes with light), the scientists were able to precisely track the exact circuit of activity in the brains cortex involved in it.

The study showed that, while mice received the Get set signal and waited for the Go sound, their motor-preparation area became active while their motor-execution area was suppressed. By inactivating the motor-preparation area, mice could not lick the nozzle after the Go sound, explains Keita Tamura, the studys other lead author. In contrast, by activating the motor-execution area, mice prematurely licked the nozzle, failing to wait until the Go sound.

The findings indicate that the Get set cue triggers both the preparation of movement and suppression of its premature execution in distinct brain regions, which enables timely reaction to the Go signal. More specifically, a part of the mouses brain called the secondary whisker motor cortex likely plays a significant role in linking sensations from the whisker to actual planning of a motor response.

Building on the present finding, we can study circuit mechanisms for how different brain areas suppress or activate each other, says Carl Petersen. This can lead us to further elucidate how we can make quick accurate movements, and how we can suppress internal impulses by cognitive control.

The authors conclude: Our results therefore point to task-epoch-specific contributions of distinct cortical regions to whisker-triggered planning of goal-directed licking and timely execution of planned lick responses.

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