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▎WuXi AppTec Content Team Editor When you start to make an action, such as picking up your coffee, starting to type in front of the computer, or even opening this article with your phone, a dopamine storm begins in your brain
.
What we may know about dopamine is that it can make people excited and happy, but as a neurotransmitter, it helps to regulate the activity of many brain areas, including the parts that control the above actions
.
According to conventional logic, the way a thing wants to be done normally is best to do it from start to finish
.
Scientists also think the same way about the working mechanism of dopamine neurons.
After the dendrites at one end of these neurons receive a signal from the external environment, they will begin to integrate the signal inside the neuron, and then begin to transmit action potentials along the axon at the other end until end
.
These action potentials then cause the neurotransmitter to be released from the end, begin to affect the adjacent neurons, and then transmit the signal in an orderly manner
.
But the latest research in Science has found that neurons can do more than just this way.
They can even receive signals from axons that are already downstream of signal transmission, triggering dopamine without dendrites.
synthesis and transport
.
The research team focused on a brain region called the striatum, which contains a large number of neurons that integrate signal inputs to regulate our daily behavior
.
Although dopamine neurons are located in another brain region, their axons can extend into the striatum
.
The normal flow is still that the dendrites of the dopamine neuron receive the signal, then the neuron transmits the action potential to the axon, and finally the dopamine is released
.
Image credit: 123RF But acetylcholine can sometimes initiate dopamine release directly in the striatum, which scientists have not known
.
To solve this mystery, Pascal Kaeser, a professor of neurobiology at Harvard Medical School, and his colleagues managed to obtain some mouse striatum tissue.
Using a microscope, they found that there was some dopamine signaling in the tissue, but the striatum.
The axons in the body have become separated from the dopamine neurons outside
.
"It was quite shocking that in the absence of the main stimulus of the cell, the release of dopamine still occurs," explains Prof.
Kaeser.
"It's a local stimulus-induced release of dopamine
.
" Could it be the aforementioned acetylcholine? Although there are more acetylcholine signals in the striatum, dopamine tends to travel farther, and research speculates that acetylcholine may actually act to amplify dopamine signaling
.
To test this, they tried adding acetylcholine and some similar drugs to the axonal portion of dopamine neurons, which quickly triggered action potentials in the dopamine neurons, which eventually led to the release of dopamine
.
Acetylcholine initiates a chain of events by binding to receptors on axons
.
▲When mice move their heads, dopamine and acetylcholine signals are dynamically associated (Image source: Reference [2]) This not only shows that the dopamine release instruction does not need to be executed from start to finish, "If you are in the axon, Sufficient acetylcholine is provided, and dendrites are no longer needed," says Professor Kaeser
.
In mouse behavioral observations, when the mice moved their heads, the acetylcholine signal slightly preceded the dopamine signal
.
Once the axonal acetylcholine receptors were destroyed, dopamine levels in the mouse striatum dropped
.
Dr.
Changliang Liu, the first author and co-corresponding author of the paper, added that this mechanism can ensure the synchronous release of dopamine and acetylcholine in the local area, and the mechanism may be broad-spectrum, because not only the terminals of dopamine neurons express acetylcholine receptors
.
The discovery of this mechanism also raises a fundamental question: Is it possible that the primary role of these receptors is to generate action potentials on nerve endings? Of course, the researchers say more evidence is needed to explain how this mechanism works in real animal behavior, "but we can be sure that it does exist in animals," says Prof.
Kaeser, who points out that understanding how dopamine is released will also help Contributes to researchers' understanding of neurological diseases including Parkinson's disease
.
Dr.
Liu Changliang believes that in theory, even when dopamine neurons die, dopamine can still be released by stimulating axons
.
But in practice, the axons cannot survive for long after the main body of dopamine neurons dies, and in the case of Parkinson's disease, the death of dopamine neurons often starts from the axons, which is a bit tricky
.
However, the study has clarified the regulation of dopamine neurons and acetylcholine, which will help to further deepen the understanding of neurotransmitters in the future.
Based on the understanding of motor initiation, it will also bring more pathological theories and treatment plans
.
After reading this article, it is no surprise that your brain has just experienced the dopamine release process discovered by the new results of "Science".
Do you feel like you are involved in a big project? Reference: [1] Firing it up.
Retrieved Mar 24th, 2022 from https:// An action potential initiation mechanism in distal axons for the control of dopamine release.
Science (2022), DOI: 10.
1126/science.
abn0532
.
What we may know about dopamine is that it can make people excited and happy, but as a neurotransmitter, it helps to regulate the activity of many brain areas, including the parts that control the above actions
.
According to conventional logic, the way a thing wants to be done normally is best to do it from start to finish
.
Scientists also think the same way about the working mechanism of dopamine neurons.
After the dendrites at one end of these neurons receive a signal from the external environment, they will begin to integrate the signal inside the neuron, and then begin to transmit action potentials along the axon at the other end until end
.
These action potentials then cause the neurotransmitter to be released from the end, begin to affect the adjacent neurons, and then transmit the signal in an orderly manner
.
But the latest research in Science has found that neurons can do more than just this way.
They can even receive signals from axons that are already downstream of signal transmission, triggering dopamine without dendrites.
synthesis and transport
.
The research team focused on a brain region called the striatum, which contains a large number of neurons that integrate signal inputs to regulate our daily behavior
.
Although dopamine neurons are located in another brain region, their axons can extend into the striatum
.
The normal flow is still that the dendrites of the dopamine neuron receive the signal, then the neuron transmits the action potential to the axon, and finally the dopamine is released
.
Image credit: 123RF But acetylcholine can sometimes initiate dopamine release directly in the striatum, which scientists have not known
.
To solve this mystery, Pascal Kaeser, a professor of neurobiology at Harvard Medical School, and his colleagues managed to obtain some mouse striatum tissue.
Using a microscope, they found that there was some dopamine signaling in the tissue, but the striatum.
The axons in the body have become separated from the dopamine neurons outside
.
"It was quite shocking that in the absence of the main stimulus of the cell, the release of dopamine still occurs," explains Prof.
Kaeser.
"It's a local stimulus-induced release of dopamine
.
" Could it be the aforementioned acetylcholine? Although there are more acetylcholine signals in the striatum, dopamine tends to travel farther, and research speculates that acetylcholine may actually act to amplify dopamine signaling
.
To test this, they tried adding acetylcholine and some similar drugs to the axonal portion of dopamine neurons, which quickly triggered action potentials in the dopamine neurons, which eventually led to the release of dopamine
.
Acetylcholine initiates a chain of events by binding to receptors on axons
.
▲When mice move their heads, dopamine and acetylcholine signals are dynamically associated (Image source: Reference [2]) This not only shows that the dopamine release instruction does not need to be executed from start to finish, "If you are in the axon, Sufficient acetylcholine is provided, and dendrites are no longer needed," says Professor Kaeser
.
In mouse behavioral observations, when the mice moved their heads, the acetylcholine signal slightly preceded the dopamine signal
.
Once the axonal acetylcholine receptors were destroyed, dopamine levels in the mouse striatum dropped
.
Dr.
Changliang Liu, the first author and co-corresponding author of the paper, added that this mechanism can ensure the synchronous release of dopamine and acetylcholine in the local area, and the mechanism may be broad-spectrum, because not only the terminals of dopamine neurons express acetylcholine receptors
.
The discovery of this mechanism also raises a fundamental question: Is it possible that the primary role of these receptors is to generate action potentials on nerve endings? Of course, the researchers say more evidence is needed to explain how this mechanism works in real animal behavior, "but we can be sure that it does exist in animals," says Prof.
Kaeser, who points out that understanding how dopamine is released will also help Contributes to researchers' understanding of neurological diseases including Parkinson's disease
.
Dr.
Liu Changliang believes that in theory, even when dopamine neurons die, dopamine can still be released by stimulating axons
.
But in practice, the axons cannot survive for long after the main body of dopamine neurons dies, and in the case of Parkinson's disease, the death of dopamine neurons often starts from the axons, which is a bit tricky
.
However, the study has clarified the regulation of dopamine neurons and acetylcholine, which will help to further deepen the understanding of neurotransmitters in the future.
Based on the understanding of motor initiation, it will also bring more pathological theories and treatment plans
.
After reading this article, it is no surprise that your brain has just experienced the dopamine release process discovered by the new results of "Science".
Do you feel like you are involved in a big project? Reference: [1] Firing it up.
Retrieved Mar 24th, 2022 from https:// An action potential initiation mechanism in distal axons for the control of dopamine release.
Science (2022), DOI: 10.
1126/science.
abn0532
