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Written by ︱ Yu Bin, editor in charge ︱ Sizhen Wang, rhythmic movements (such as walking, breathing, etc.
) are generally driven by a central pattern generator (CPG) loop composed of interneurons [1]
.
A CPG is an autonomous neuron or neural network that produces rhythmic neural electrical activity outputs in the absence of sensory or descending inputs [2]
.
Due to the high degree of evolutionary conservation, CPGs are widely present in the nervous systems of vertebrates and invertebrates [3]
.
Gao Shangbang’s research group and colleagues in the field recently discovered that excitatory A motor neurons (A-MNs) in nematode form a distributed oscillator network similar to CPG, revealing the motor neuron oscillator for the first time [4] -6] can also drive motor rhythms (Fig.
1)
.
However, how rhythmic activity patterns are structured by motor neuron oscillators, and the molecular basis behind this, remains unclear
.
Fig.
1 Schematic diagram of the movement model of C.
elegans as a dynamic coupling of various movement states
.
(Picture quoted from: Quan Wen et al.
, Philos Trans R Soc Lond B Biol Sci, 2018) On March 16, 2022, Gao Shangbang’s research group from the School of Life Science and Technology, Huazhong University of Science and Technology, published in Frontiers of Molecular Neuroscience ( Frontiers in Molecular Neuroscience) published a research paper titled "Motor Rhythm Dissection from the Backward Circuit in C.
elegans", revealing how the oscillatory properties of motor neuron oscillators are structured at the molecular cellular level
.
Doctoral student Yu Bin is the first author, doctoral student Wang Ya is the second author, and Professor Gao Shangbang is the corresponding author
.
In this study, the authors found that the rhythmic postsynaptic currents (rPSCs) output by motor neurons actually consist of multiple components, and at least six different ion channels are involved in the regulation of A-MNs-rPSCs
.
C.
elegans excitatory class A motor neurons mediate backward locomotion
.
Using optogenetic techniques to isolate pure receding motor loops, the authors used in vivo electrophysiological techniques to record electrical signals from muscle cells, and found that nematode type A motor neuron oscillatory electrical activity is actually composed of three distinct groups of rhythmic firing (rPSCs) They are divided into phasic-type for fast discharge, tonic-type for slower discharge, and long-lasting-type for long-term discharge (Fig.
2)
.
Figure 2.
Three types of composite rPSCs constitute type A motor neuron oscillator CPGs
.
(Source: Yu Bin et al.
, Front in Mol Neurosci, 2022) It is known that neuron firing depends on various ion channels on the nerve cell membrane, such as voltage-gated sodium ion, calcium ion channel and inhibitory potassium ion channel, etc.
.
Combining the advantages of nematode molecular genetic mutant screening, the authors found that two voltage-gated calcium channels, EGL-19 (L-type voltage-gated calcium channel) and UNC-2 (P, Q-type voltage-gated calcium channel), had significant effects on the above-mentioned A- MNs-rPSCs are positively regulated, specifically, in egl-19 loss-of-function mutants, tonic-type rPSCs have significantly reduced firing frequency and firing volume, while in egl-19 function-enhanced mutants, the firing rate is slower.
The firing volume of tonic-type rPSCs was significantly increased, suggesting that the L-type voltage-gated calcium channel EGL-19 plays an important role in tonic-type rPSCs
.
In the same way, the P,Q-type voltage-gated calcium channel UNC-2 was found to have effects on both tonic- and phasic rPSCs
.
Interestingly, the authors also found that the voltage-independent sodium ion drain channel NCA (sodium ion drain channel) positively regulates all three rPSCs, indicating that different rhythm discharges have different molecular mechanisms
.
Indeed, the authors further analyzed multiple inhibitory potassium channel mutants and found that the large-conductance voltage-gated potassium channel SLO-1 specifically regulates tonic- and phasic-type rPSCs, while sodium ion-activated potassium channel SLO-2, voltage The gated potassium channel SHL-1 inhibits tonic- and long-lasting-type rPSCs to varying degrees
.
Therefore, this study initially revealed part of the working mechanism of motor neuron oscillators at the molecular and cellular level (Figure 3)
.
Fig.
3 Effects of different ion channels on rPSCs and their behavior
.
(Picture quoted from: Yu Bin et al.
, Front Mol Neuroscie, 2022) Conclusion and discussion, inspiration and prospect of the article In summary, this study combines optogenetic, electrophysiological and molecular genetic techniques to analyze the motor neuron oscillator The molecular composition of the central pattern generator (CPG), and the following important conclusions are obtained: (1) Three types of rhythmic discharge constitute the rhythmic activity of motor neuron oscillators
.
(2) Rhythmic discharge essentially regulates the backward movement of nematodes
.
(3) A variety of different Ca2+, Na+ and K+ channels regulate different types of rhythmic discharge patterns
.
(4) The multifunctional regulation of rhythmic discharge by different ion channels significantly affects the speed of backward movement by increasing or decreasing the frequency and/or charge of rhythmic discharge
.
How do motor neurons coordinate different types of rhythmic firing patterns? The authors speculate that each motor neuron is capable of generating all types of rhythmic firing patterns, but the details of the specific working patterns require further study
.
This study demonstrates that motor neurons generate three types of rhythmic firings that drive receding rhythmic movements, and that these rhythmic firings can occur individually or simultaneously, but without a clear sequential relationship
.
Whether the generation of rhythmic discharges is phase-regular or spontaneous, and how the sequence of discharges determines receding rhythmic movements is largely unknown
.
In the experiments, the authors also observed transient discharge phenomena different from those of rPSCs or mPSCs
.
The relationship between these discharge events is currently unclear and requires further exploration
.
In conclusion, this study revealed that motor neuron oscillators produce various types of rhythmic discharges.
Different rhythmic discharges require the participation of multiple channels.
Changes in the frequency and charge of rhythmic discharges can affect movement speed
.
Link to the original text: https://doi.
org/10.
3389/fnmol.
2022.
845733 The first author Yu Bin (the second from the left in the first row), the second author Wang Ya (the second from the left in the second row), and the corresponding author Gao Shangbang (the fifth from the left in the second row) (Photo provided by: Gao Shangbang Research Group, Huazhong University of Science and Technology) Gao Shangbang, Ph.
D.
, professor and doctoral supervisor of the School of Life Science and Technology, Huazhong University of Science and Technology
.
Relying on the Key Laboratory of Molecular Biophysics of the Ministry of Education, the research focuses on the neural circuits and molecular mechanisms that generate, maintain and regulate exercise
.
The research team is carrying out further research work on the mechanism of motor conduction rate and whole-brain imaging.
Interested graduate students and postdoctoral fellows are welcome to join us! Please email: sgao@hust.
edu.
cn
.
(http://faculty.
hust.
edu.
cn/gaoshangbang/zh_CN/index.
htm) Selected articles from previous issues [1] Review of Nat Neurosci︱Two-photon holographic optogenetics to detect neural coding [2] Mol Psychiatry︱ Biological clock The role of gene Bmal1 in a mouse model of autism and cerebellar ataxia [3] Science︱ mouse rapid eye movement sleep is regulated by dopamine signaling in the basolateral amygdala [4] Nat Neurosci︱ amygdala in patients with bipolar disorder Down-regulation of neuroimmunity and synapse-related pathways in and anterior cingulate [5] Nat Commun︱ Zhou Xiaoming/Sun Ziyi's team revealed the molecular mechanism of Sigma-1 receptor's ligand entry pathway based on its open conformation [6] Glia︱ Yuan Zengqiang project The group revealed a new mechanism for regulating the proliferation of oligodendrocyte precursor cells: c-Abl phosphorylates Olig2 [7] HBM︱ Yu Lianchun’s research group revealed the relationship between the brain avalanche critical phenomenon and fluid intelligence and working memory [8] J Neuroinflammation︱ Gu Xiaoping’s research The group revealed the important role of astrocyte network in the long-term isoflurane anesthesia-mediated postoperative cognitive dysfunction【9】Nat Methods︱Fei Peng/Zhang Yuhui research group reported live cell super-resolution imaging research New progress [10] J Neurosci︱ Zhou Qiang's research group revealed that extrasynaptic NMDARs bidirectionally regulate intrinsic excitability of inhibitory neurons [1] Scientific research skills︱ The 4th near-infrared brain function data analysis class (online) : 2022.
4.
18~4.
30) [2] Scientific Research Skills︱Introduction to Magnetic Resonance Brain Network Analysis (Online: 2022.
4.
6~4.
16) [3] Training Course︱Scientific Research Mapping·Academic Image Special Training [4] Single-cell sequencing and Symposium on Spatial Transcriptomics Data Analysis (2022.
4.
2-3 Tencent Online) References (swipe up and down to view) 1, Grillner, S.
(2006).
Biological pattern generation: the cellular and computational logic of networks in motion.
Neuron 52 , 751-766.
2, Marder, E.
, and Bucher, D.
(2001).
Central pattern generators and the control of rhythmic movements.
Current biology: CB 11, R986-996.
3, Katz, PS (2016).
Evolution of central pattern generators and rhythmic behaviors.
Philosophical Transactions of the Royal Society of London.
Series B, Biological Sciences , 371, 20150057.
4, Gao, S.
, Guan, SA, Fouad, AD, Meng, J.
, Kawano, T.
, Huang, YC, Li, Y.
, Alcaire, S.
, Hung, W.
, Lu, Y .
, et al.
(2018).
Excitatory motor neurons are local oscillators for backward locomotion.
eLife 7.
10.
7554/eLife.
29915.
5, Xu, T.
, Huo, J.
, Shao, S.
, Po, M.
, Kawano, T.
, Lu, Y.
, Wu, M.
, Zhen, M.
, and Wen, Q.
(2018).
Descending pathway facilitates undulatory wave propagation in Caenorhabditis elegans through gap junctions.
Proceedings of the National Academy of Sciences of the United States of America 115, E4493-e4502.
6, Wen, Q.
, Gao, S.
, and Zhen, M.
(2018).
Caenorhabditis elegans excitatory ventral cord motor neurons derive rhythm for body undulation.
Philosophical transactions of the Royal Society of London.
Series B, Biological sciences 373.
Edition by Wang Sizhen
) are generally driven by a central pattern generator (CPG) loop composed of interneurons [1]
.
A CPG is an autonomous neuron or neural network that produces rhythmic neural electrical activity outputs in the absence of sensory or descending inputs [2]
.
Due to the high degree of evolutionary conservation, CPGs are widely present in the nervous systems of vertebrates and invertebrates [3]
.
Gao Shangbang’s research group and colleagues in the field recently discovered that excitatory A motor neurons (A-MNs) in nematode form a distributed oscillator network similar to CPG, revealing the motor neuron oscillator for the first time [4] -6] can also drive motor rhythms (Fig.
1)
.
However, how rhythmic activity patterns are structured by motor neuron oscillators, and the molecular basis behind this, remains unclear
.
Fig.
1 Schematic diagram of the movement model of C.
elegans as a dynamic coupling of various movement states
.
(Picture quoted from: Quan Wen et al.
, Philos Trans R Soc Lond B Biol Sci, 2018) On March 16, 2022, Gao Shangbang’s research group from the School of Life Science and Technology, Huazhong University of Science and Technology, published in Frontiers of Molecular Neuroscience ( Frontiers in Molecular Neuroscience) published a research paper titled "Motor Rhythm Dissection from the Backward Circuit in C.
elegans", revealing how the oscillatory properties of motor neuron oscillators are structured at the molecular cellular level
.
Doctoral student Yu Bin is the first author, doctoral student Wang Ya is the second author, and Professor Gao Shangbang is the corresponding author
.
In this study, the authors found that the rhythmic postsynaptic currents (rPSCs) output by motor neurons actually consist of multiple components, and at least six different ion channels are involved in the regulation of A-MNs-rPSCs
.
C.
elegans excitatory class A motor neurons mediate backward locomotion
.
Using optogenetic techniques to isolate pure receding motor loops, the authors used in vivo electrophysiological techniques to record electrical signals from muscle cells, and found that nematode type A motor neuron oscillatory electrical activity is actually composed of three distinct groups of rhythmic firing (rPSCs) They are divided into phasic-type for fast discharge, tonic-type for slower discharge, and long-lasting-type for long-term discharge (Fig.
2)
.
Figure 2.
Three types of composite rPSCs constitute type A motor neuron oscillator CPGs
.
(Source: Yu Bin et al.
, Front in Mol Neurosci, 2022) It is known that neuron firing depends on various ion channels on the nerve cell membrane, such as voltage-gated sodium ion, calcium ion channel and inhibitory potassium ion channel, etc.
.
Combining the advantages of nematode molecular genetic mutant screening, the authors found that two voltage-gated calcium channels, EGL-19 (L-type voltage-gated calcium channel) and UNC-2 (P, Q-type voltage-gated calcium channel), had significant effects on the above-mentioned A- MNs-rPSCs are positively regulated, specifically, in egl-19 loss-of-function mutants, tonic-type rPSCs have significantly reduced firing frequency and firing volume, while in egl-19 function-enhanced mutants, the firing rate is slower.
The firing volume of tonic-type rPSCs was significantly increased, suggesting that the L-type voltage-gated calcium channel EGL-19 plays an important role in tonic-type rPSCs
.
In the same way, the P,Q-type voltage-gated calcium channel UNC-2 was found to have effects on both tonic- and phasic rPSCs
.
Interestingly, the authors also found that the voltage-independent sodium ion drain channel NCA (sodium ion drain channel) positively regulates all three rPSCs, indicating that different rhythm discharges have different molecular mechanisms
.
Indeed, the authors further analyzed multiple inhibitory potassium channel mutants and found that the large-conductance voltage-gated potassium channel SLO-1 specifically regulates tonic- and phasic-type rPSCs, while sodium ion-activated potassium channel SLO-2, voltage The gated potassium channel SHL-1 inhibits tonic- and long-lasting-type rPSCs to varying degrees
.
Therefore, this study initially revealed part of the working mechanism of motor neuron oscillators at the molecular and cellular level (Figure 3)
.
Fig.
3 Effects of different ion channels on rPSCs and their behavior
.
(Picture quoted from: Yu Bin et al.
, Front Mol Neuroscie, 2022) Conclusion and discussion, inspiration and prospect of the article In summary, this study combines optogenetic, electrophysiological and molecular genetic techniques to analyze the motor neuron oscillator The molecular composition of the central pattern generator (CPG), and the following important conclusions are obtained: (1) Three types of rhythmic discharge constitute the rhythmic activity of motor neuron oscillators
.
(2) Rhythmic discharge essentially regulates the backward movement of nematodes
.
(3) A variety of different Ca2+, Na+ and K+ channels regulate different types of rhythmic discharge patterns
.
(4) The multifunctional regulation of rhythmic discharge by different ion channels significantly affects the speed of backward movement by increasing or decreasing the frequency and/or charge of rhythmic discharge
.
How do motor neurons coordinate different types of rhythmic firing patterns? The authors speculate that each motor neuron is capable of generating all types of rhythmic firing patterns, but the details of the specific working patterns require further study
.
This study demonstrates that motor neurons generate three types of rhythmic firings that drive receding rhythmic movements, and that these rhythmic firings can occur individually or simultaneously, but without a clear sequential relationship
.
Whether the generation of rhythmic discharges is phase-regular or spontaneous, and how the sequence of discharges determines receding rhythmic movements is largely unknown
.
In the experiments, the authors also observed transient discharge phenomena different from those of rPSCs or mPSCs
.
The relationship between these discharge events is currently unclear and requires further exploration
.
In conclusion, this study revealed that motor neuron oscillators produce various types of rhythmic discharges.
Different rhythmic discharges require the participation of multiple channels.
Changes in the frequency and charge of rhythmic discharges can affect movement speed
.
Link to the original text: https://doi.
org/10.
3389/fnmol.
2022.
845733 The first author Yu Bin (the second from the left in the first row), the second author Wang Ya (the second from the left in the second row), and the corresponding author Gao Shangbang (the fifth from the left in the second row) (Photo provided by: Gao Shangbang Research Group, Huazhong University of Science and Technology) Gao Shangbang, Ph.
D.
, professor and doctoral supervisor of the School of Life Science and Technology, Huazhong University of Science and Technology
.
Relying on the Key Laboratory of Molecular Biophysics of the Ministry of Education, the research focuses on the neural circuits and molecular mechanisms that generate, maintain and regulate exercise
.
The research team is carrying out further research work on the mechanism of motor conduction rate and whole-brain imaging.
Interested graduate students and postdoctoral fellows are welcome to join us! Please email: sgao@hust.
edu.
cn
.
(http://faculty.
hust.
edu.
cn/gaoshangbang/zh_CN/index.
htm) Selected articles from previous issues [1] Review of Nat Neurosci︱Two-photon holographic optogenetics to detect neural coding [2] Mol Psychiatry︱ Biological clock The role of gene Bmal1 in a mouse model of autism and cerebellar ataxia [3] Science︱ mouse rapid eye movement sleep is regulated by dopamine signaling in the basolateral amygdala [4] Nat Neurosci︱ amygdala in patients with bipolar disorder Down-regulation of neuroimmunity and synapse-related pathways in and anterior cingulate [5] Nat Commun︱ Zhou Xiaoming/Sun Ziyi's team revealed the molecular mechanism of Sigma-1 receptor's ligand entry pathway based on its open conformation [6] Glia︱ Yuan Zengqiang project The group revealed a new mechanism for regulating the proliferation of oligodendrocyte precursor cells: c-Abl phosphorylates Olig2 [7] HBM︱ Yu Lianchun’s research group revealed the relationship between the brain avalanche critical phenomenon and fluid intelligence and working memory [8] J Neuroinflammation︱ Gu Xiaoping’s research The group revealed the important role of astrocyte network in the long-term isoflurane anesthesia-mediated postoperative cognitive dysfunction【9】Nat Methods︱Fei Peng/Zhang Yuhui research group reported live cell super-resolution imaging research New progress [10] J Neurosci︱ Zhou Qiang's research group revealed that extrasynaptic NMDARs bidirectionally regulate intrinsic excitability of inhibitory neurons [1] Scientific research skills︱ The 4th near-infrared brain function data analysis class (online) : 2022.
4.
18~4.
30) [2] Scientific Research Skills︱Introduction to Magnetic Resonance Brain Network Analysis (Online: 2022.
4.
6~4.
16) [3] Training Course︱Scientific Research Mapping·Academic Image Special Training [4] Single-cell sequencing and Symposium on Spatial Transcriptomics Data Analysis (2022.
4.
2-3 Tencent Online) References (swipe up and down to view) 1, Grillner, S.
(2006).
Biological pattern generation: the cellular and computational logic of networks in motion.
Neuron 52 , 751-766.
2, Marder, E.
, and Bucher, D.
(2001).
Central pattern generators and the control of rhythmic movements.
Current biology: CB 11, R986-996.
3, Katz, PS (2016).
Evolution of central pattern generators and rhythmic behaviors.
Philosophical Transactions of the Royal Society of London.
Series B, Biological Sciences , 371, 20150057.
4, Gao, S.
, Guan, SA, Fouad, AD, Meng, J.
, Kawano, T.
, Huang, YC, Li, Y.
, Alcaire, S.
, Hung, W.
, Lu, Y .
, et al.
(2018).
Excitatory motor neurons are local oscillators for backward locomotion.
eLife 7.
10.
7554/eLife.
29915.
5, Xu, T.
, Huo, J.
, Shao, S.
, Po, M.
, Kawano, T.
, Lu, Y.
, Wu, M.
, Zhen, M.
, and Wen, Q.
(2018).
Descending pathway facilitates undulatory wave propagation in Caenorhabditis elegans through gap junctions.
Proceedings of the National Academy of Sciences of the United States of America 115, E4493-e4502.
6, Wen, Q.
, Gao, S.
, and Zhen, M.
(2018).
Caenorhabditis elegans excitatory ventral cord motor neurons derive rhythm for body undulation.
Philosophical transactions of the Royal Society of London.
Series B, Biological sciences 373.
Edition by Wang Sizhen
