Nature: "Worthy" motor development, can't be turned off by nature?

Click on the blue word to pay attention to the activity of the neural circuit in the critical period of our development.
It can change the morphological characteristics of neurons and produce permanent changes to the circuit structure and brain function.

Disorders in this period are considered to be an important pathogenesis of neurodevelopmental disorders such as autism spectrum disorders and schizophrenia.

During the critical period of development, neuronal connections can be reshaped in many ways, one of which is called steady-state plasticity, where the entire neuron undergoes qualitative changes (changes in the number of dendrites, synapses, and transmission functions).

Although homeostatic plasticity can occur in the adult brain, most activity-dependent remodeling peaks in early development.

On April 7, 2021, the research team of Chris Q.
Doe and Sarah D.
Ackerman of the Neuroscience Institute of the Howard Hughes Medical Institute at the University of Oregon published an article in the journal Nature revealing that astrocytes act as a key “mediator of neuronal plasticity” ", to achieve the correct closure during the critical period of development.

The critical period of motor nerve circuit development is 8 hours after the hatching of Drosophila larvae.
Drosophila aCC and RP2 motor neurons are prone to activity-dependent remodeling.
Therefore, the researchers selected these two types of neurons as the research model and found that the motor nerve ring The critical period of road development is closed 8 hours after the larva hatches.
The specific result is: after inhibiting the motor neuron in the last hour of embryonic formation, its dendritic volume increases significantly, and after activating the motor neuron, it causes the loss of dendrites; but After the larvae hatched for 8 hours, the aforementioned effects of inhibiting or activating motor neurons on dendrites no longer exist.

Inhibition or activation of neurons causes morphological changes of neuron dendrites.
Generally speaking, in vertebrates, steady-state plasticity can occur within a few hours or days.

The researchers found that in Drosophila, the motor neuron was inhibited for 15 minutes, 1 hour and 4 hours during the embryonic stage.
The result was that only 1 hour and 4 hours of inhibition could cause dendritic morphological changes, and 15 minutes of activation could cause the tree.
Sudden changes.

Optical imaging experiments further confirmed that axons began to retract 12 minutes after light-activated motor neurons.

These results indicate that activity-induced remodeling of Drosophila motor neurons can occur in just a few minutes, much faster than previously reported mammalian steady-state plasticity.

The activity-dependent remodeling of motor nerve circuits during the critical period of development is also reflected in excitatory input and inhibitory input.

The researchers further found that after 1 hour of inhibiting motor neuron activity, the number of inhibitory synapses decreased and the number of excitatory synapses increased; on the contrary, the number of excitatory synapses decreased after activating motor neurons, but the number of inhibitory synapses decreased.
The number of touches has no effect.

This indicates that motor neurons dynamically adjust excitatory and inhibitory inputs according to their activity levels during the critical period of development.

Astrocytes regulate the normal shutdown of critical periods of development.
Studies have shown that Drosophila astrocytes “enclose” nerve fibers in the later stages of embryonic development.

Researchers found that with the end of the critical period of development, motor neuron synapses are gradually enveloped by astrocytes.

At the same time, after knocking out astrocytes, the morphology of dendrites still changed dynamically 8 hours after the larvae hatched, which was completely different from normal conditions and caused dyskinesia.

This indicates that astrocytes may participate in the normal closing process of the key developmental phase of the motor nerve circuit.

In order to further find the molecular mechanism of astrocytes regulating the normal shutdown of the critical period of development, they revealed through single-cell sequencing that 4 genes such as gat, chpf, Neuroligins (Nlg) 4 and Nlg 2 are motor nerve loops in the time dimension.
Necessary for the normal closure of the critical period of road development.

Neuroligins are cell adhesion proteins that can regulate astrocyte morphogenesis and bind to the cell surface protein Neurexins 1 (Nrx-1).

The researchers used RNA interference technology to knock down Nrx-1 and prolonged the closing time of the critical period of motor nerve circuit development.
In addition, Nlg 2-Nrx-1 was expressed in astrocytes and neuron trees in the form of receptor ligands.
Suddenly.

At the same time, Nrx-1 can promote the stability of motor neuron axon microtubules.

This indicates that the Nlg 2-Nrx-1 signal achieves the normal closure of the critical period of development by stabilizing the microtubule structure of the dendrites.

In summary, this article reveals that astrocytes regulate the microtubule structure of dendrites through Nlg 2-Nrx-1 signals, so as to efficiently close the critical period of motor nerve circuit development during a specific period and maintain normal motor functions.

[References] 1.
https://doi.
org/10.
1038/s41586-021-03441-2 The pictures in the article are all from the references