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Editor-in-charge | Xi
The hand is a very important organ, not only humans, many mammals use the hand to communicate
with the outside world.
We can accurately aim at the target with our hands, such as hitting a fast-moving ping-pong ball by controlling the movement of our hands; We can also manipulate objects with dexterity with our hands, such as playing the piano
with our fingers.
It can be seen that aiming and manipulation are the two main functions of the upper limbs (including the hands), and in order to achieve these two functions, we must control the contraction
of the upper limb muscles through the neural circuits composed of specific nerve cells.
Existing studies have shown that exercise-related neural circuits span multiple regions, from the brain to the spinal cord [1].
Some of these neural circuits are distributed in the hindbrain including the brainstem and spinal cord, responsible for sending nerve signals to control muscle activity to perform motor functions; There are also neural circuits located in the cerebral cortex and basal ganglia, which are responsible for integrating various information such as motor sensation and issuing signals to control the downstream neural circuits [2].
Recent studies have determined that neurons located in specific regions of the medulla in the brainstem can act like an exchange switchboard, select different medulla neural circuits and control multiple upper extremity motor functions [3].
。 So, how do these upper limb movement-related medulla oblongata neurons send signals at specific times and in the right way to accurately guide the upper limb to perform motor functions? The cerebral cortex, because of its extensive neural pathways projecting into the medulla oblongata, can influence and regulate neural circuits in several different brain regions to complete the processing
of motor signals.
Therefore, understanding the connection logic between motor neural circuits in different regions of the nervous system, especially how nerve signals in the cerebral cortex are transmitted to the medulla oblongata, is essential
to further explore the neural basis of upper limb motor function, as well as to study the learning mechanism of movement, and even promote the recovery of motor function after injury.
On January 5, 2023, the Silvia Arber group of the Biozentrum and Friedrich Miescher Institute at the University of Basel in Switzerland (Yang Wuzhou as the first author) was present at Cell The journal published an article entitled Structural and functional map for forelimb movement phases between cortex and medulla, which anatomically analyzed the structure of the neural pathway between the cerebral cortex and the brainstem medulla oblongata.
It also reveals the important role
played by specific cerebral cortex-medullary nerve projection in controlling the aiming and manipulation functions of upper limb movement.
First, to determine which neurons in the cerebral cortex can directly communicate with the medullary nerve circuits associated with upper limb movement, the authors utilized retrograde AAV with fluorescently labeled retrograde AAV [4].
。 The virus can infect neurons through axons, so it can label neurons
that project to specific regions.
The authors injected this AAV into the lomobile-related medulla oblongata region of the upper extremities and found that cerebral cortex-medullary projection neurons were mainly distributed in the anterior cerebral
cortex.
By comparing it with the distribution area of cerebral cortex-spinal projection neurons, the authors found that in the anterior cerebral cortex, the medial region (MAC) has both cerebral cortex-medulla oblongata and cerebral cortex-spinal projection neurons, while the lateral region (LAC) has only cerebral cortex-medulla oblongata projection neurons
.
From this, the authors determined that different regions of the cerebral cortex have different projection neurons, and how do these cerebral cortical regions communicate with the medulla oblongata? To investigate whether different regions of the cerebral cortex have specific cerebral cortex-medullary nerve projections, the authors used anterograde tracing adeno-associated viruses to label synapses of neurons in the cerebral cortex in specific regions
.
Interestingly, the authors found that MAC projects to the ventral medulla oblongata and LAC projects to the dorsal medulla oblongata, and not only that, but this topological projection is consistent throughout the medulla oblongata from anterior to posterior, whereby the synapses of the cerebral cortex project to the medulla oblongata form a three-dimensional columnar structure
.
This anatomical structure suggests specific cerebral cortex-medullary nerve pathways and demonstrates fine partitioning
of the cerebral cortex.
Figure 1: Three-dimensional structure of the cerebral cortex to the medulla oblongata nerve projection So, is this fine cerebral cortical partition functionally significant?
To determine the role of different cerebral cortical regions in upper limb movement, the authors trained mice to reach out and aim at grabbing food pellets
.
Interestingly, when MAC was temporarily inactivated, mice lost the ability to reach out, but LAC temporary inactivation and the control group had no effect
on reach movement.
Mice on the other hand, manipulate food
with both hands when they catch and eat food pellets.
Surprisingly, compared with the MAC temporary inactivation and the control group, the LAC temporary inactivation made the mice tend not to use both hands to manipulate the food pellets, and even when the mice used their hands, the LAC temporarily inactivated mice still could not manipulate the food pellets
well.
From this, the authors conclude that MAC and LAC play a necessary role
, respectively, in controlling aiming and manoeuvring of upper limb movements.
Video 1:MAC is reaching for aimplays a necessary role
.
:top: control; Bottom: MAC inactivation
.
Video 2: LAC plays a necessary role when manipulating with both hands.
Top: control; Bottom: LAC inactivation
.
A further question becomes, are specific functions of the cerebral cortex related to neural circuits in the medulla oblongata? To answer this question, the authors first used adeno-associated viruses labeled across neurons to observe postsynaptic neurons in the medulla oblongata that receive cerebral cortical projections [5].
The results showed that these postsynaptic neurons in the medulla oblongata were similar to those from the cerebral cortex, suggesting that different medulla oblongata neurons received signals
from specific cerebral cortex.
Further, the authors recorded the activity of cortically regulated medullary oblongata neurons by electrophysiology recording the firing activity
of upper limb motor associated medullary neurons in vivo multichannel silicon electrodes on free-moving mice, and using optogenetic expression of photosensitive ion channels to stimulate different cortical regions.
While recording neuronal activity, mice were also performing a series of movements of reaching out to grab food pellets and manipulating food pellets with both hands to eat, so that the activity of medullary neurons could be correlated with the upper limb movement behavior of mice
.
Interestingly, MAC-regulated medullary neurons were mostly associated with mice reaching for food, while LAC-regulated medatara neurons produced firing activity
when mice manipulated food pellets.
The results of this experiment show that different regions of the cerebral cortex transmit nerve signals to specific medulla oblongata neurons, and these specific medulla oblongata neurons are involved in upper limb movements
at different times, from aiming to manipulation.
In summary, this study revealed the fine partitioning of the cerebral cortex and found that there is a specific neural connection structure between the cerebral cortex and the medulla oblongata, and these cerebral cortex-medullary nerve pathways accurately regulate a series of upper limb movements
from aiming to manipulation.
The authors further showed that this highly specialized cerebral cortical neural projection pathway not only exists in the medulla oblongata, but can also be extended to more movement-related regions, providing a basis
for further research on the neural control mechanism of upper limb movement.
Original link:
https://doi.
org/10.
1016/j.
cell.
2022.
12.
009
Platemaker: Eleven
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