"Nature Communications" publishes the research results of the Center for Brain Excellence on the loop mechanism of motor planning

On May 11, 2021, the journal Nature Communications published an online research paper titled "The Mechanism of the Superior Cortical Circuit in Memory-Dependent Perception Decision-Making Tasks".
The research was developed by the Chinese Academy of Sciences' Brain Science and Intelligent Technology Excellence Innovation Completed by Xu Ninglong's research group from the Center (Institute of Neuroscience), Shanghai Center for Brain Science and Brain-like Research, and State Key Laboratory of Neuroscience.

This research analyzes the loop function from the secondary motor cortex to the upper colliculus, reveals its key role in decision-related motion planning and its information processing mechanism.

In order to survive in nature, organisms do not need to respond to external environmental stimuli all the time.
Instead, they often need to temporarily store the received stimulus information in the brain and plan the necessary responses at the same time.

For example, when hunting on the grassland, a cheetah needs to lurch in the grass and slowly approach its prey until it jumps up at the right time.
Before the prey can react, it will catch up and knock it down.

If the timing is not right and the exercise preparation is not adequate, the prey is likely to escape under the nose.

The cheetah is actually undergoing movement planning in the process of preparing to launch an offense.

In this case, exercise planning directly affects the survival of the animal; and in many other adaptive behaviors, exercise planning also plays an important role.

So how does the brain realize the planning of future actions? Which brain regions and neural circuits use what mechanisms to achieve motor planning? Previous studies have found that the anterolateral motor cortex (part of the secondary motor cortex) plays an important role in motor planning.

A series of subsequent studies analyzed that a large number of other brain regions related to the motor cortex, such as the thalamus, basal ganglia, and cerebellum, are involved in motor planning.

However, because these brain regions form a very complex network system, exerting an influence on any node in the network will affect the whole body and affect the dynamics of the entire network.

Therefore, analyzing the relationship between different nodes in this network and clarifying how their interaction affects motion planning is an urgent problem to be solved.

To answer this question, Duan Chunyu, a postdoctoral fellow in Xu Ninglong’s research group, and a doctoral student Pan Yuxin, used the perceptual decision-making behavior framework to establish a parametric motor planning behavior paradigm, and comprehensively used loop recording and manipulation techniques to study the secondary motor cortex in detail.
The mechanism of action of the key neural pathways to the inferior superior colliculus of the cortex.

Specific labeling of cortical to superior colliculus projection neurons.
In this new behavioral paradigm, mice need to classify the rate of tick sounds and report their classification results by licking the left or right water outlet.

The important thing is that the mouse must wait for a voice prompt before reporting, which is like a starting gun to answer.

During the waiting delay period, the mouse needs to plan the movement of the licking response.

Since the delay length and tick frequency of each trial are different, the difficulty will also be different, which provides convenience for accurately studying the contribution of neural circuits to motion planning (Figure ac).

Through optogenetic transient inhibition in different brain regions and time periods, the researchers concluded that the secondary motor cortex and the superior colliculus both play an important role in this task, and the effect of inhibiting both brain regions at the same time is greater than simply inhibiting the secondary The motor cortex suggests that the superior colliculus is not only a passive executor of the command output of the secondary motor cortex, but can further process the upstream input information and contribute to the function of planning exercise.

In order to interpret the information transmitted by the secondary motor cortex to the upper colliculus, the researchers reversely marked the cells of the secondary motor cortex that were projected to the upper colliculus, and observed the activity of these labeled neurons under a two-photon microscope.

The results showed that compared to randomly labeled cells, the group of cells that were thrown into the upper colliculus showed a stronger coding intensity of motion information, and this intensity would become stronger over time, from sound stimulation, delay, to During the licking exercise, the contralateral movement showed stronger selectivity (figure df).

These results support that the loop does carry motion planning information.

So is this information causally related to exercise planning? The researchers used chemical genetics methods to specifically inhibit the loop from the secondary motor cortex to the upper colliculus by embedding the cannula, while keeping the other downstream brain areas of the secondary motor cortex uninhibited , Found that the correct rate of mouse behavior is affected, and the extent of the effect depends on the difficulty of the sound stimulation and the length of the delay (Figure gh).

These results support that the loop from the secondary motor cortex to the superior colliculus has a causal relationship to motor planning.

To further explore how the information from the motor cortex is processed in the superior colliculus, the researchers compared the activity characteristics of excitatory cells and inhibitory cells in the task.

Because these two kinds of cells can accept projections from the secondary motor cortex and have the same intensity, both of them may further process upstream information.

Through fiber optic photometry, the researchers found that the selection information encoded by excitatory cells during the sound and delay period is more stable, which may help to maintain the information during the delay period, while inhibitory cells are more inclined to switch encoding characteristics.
Play different regulatory roles in different stages of the motion planning process (Figure ij).

In summary, this study systematically studied how a circuit from the secondary motor cortex to the subcortical structure affects motor planning, providing new experimental evidence for people to understand the neural circuit mechanism behind motor planning.

Figure 1: a, auditory alternative task, the mouse chooses to lick the left or right water spout according to the tick frequency of the sound.

b.
The time structure of the task.
After hearing the sound, the mouse needs to wait for 0.
3-1.
5 s, and hear a prompt after the delay is over, and then answer it.

c, Psychophysical curve of mouse behavior.

d, Two-photon imaging records secondary motor cortical neurons projecting to the upper colliculus.

e, The example neuron shows selectivity to animal behavior.

f, As time goes by, more and more cells show stronger selectivity.

g, Use pharmacological genetics to specifically inhibit the loop from the secondary motor cortex to the superior colliculus.

h.
After loop inhibition, the behavioral impact of mice is greater in the difficult trials of long-delay stimulation.

i.
Record the response characteristics of neuron subgroups of different cell types in the superior colliculus in the process of motor planning by using optical fiber photometry.

j.
Excitatory and inhibitory superior colliculus neurons exhibit different response characteristics in motor planning.

Under the guidance of researcher Xu Ninglong, the work was completed by postdoctoral researcher Duan Chunyu and doctoral student Pan Yuxin.
At the same time, it was greatly assisted by the Zhang Siyu research group of Shanghai Jiaotong University.
Research assistants Ma Guofen and Zhou Taotao provided important assistance in the collection of experimental data.
Other members of the research group actively participated in the discussion, and were greatly assisted by the experimental animal platform of the Brain Intelligence Center of Excellence and the optical imaging platform of the Public Technical Service Center.

The research was funded by the Ministry of Science and Technology, the National Natural Science Foundation of China, the Chinese Academy of Sciences and the Shanghai Municipal Science and Technology Commission.

Postdoctoral Duan Chunyu Ph.
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