PNAS｜Song Jianren/Hua Yunfeng jointly discovered new interneurons in the spinal cord to analyze new behavioral decision mechanisms

EditorEnzyme Beauty has started to study the neuroregulatory mechanism of behavioral (escape) decisions using the teleost Mauthner cell system as a model since the 1950s
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Over the past seven decades, these studies have brought many conceptual breakthroughs to neurobiology, such as: Motor command neurons (motor command neurons), Asymmetry gap junctions (asymmetric electrical synapse structure and function), Sensory-motor integration ( Sensorimotor integration) and so on
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However, whether the neural control mechanism behind behavioral decisions is solely derived from the "brain" or whether it is jointly determined by the "brain and spinal cord" has long been controversial
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This study uses the "brain-spinal cord" in vivo and in vitro models to explore this in depth
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Spinal motor nerve circuits are the basis for generating and executing motor behaviors
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The transient motor commands of the brain are transmitted to the spinal cord through the long axons of the reticular spinal cord neurons, activating interneurons in the spinal cord
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These activated interneurons convert brain motor commands into motor rhythms and patterns, thereby driving motor neurons to complete corresponding motor behaviors [1,2]
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Among them, spinal cord excitatory V2a interneurons (expressing transcription factor Chx10) are considered to be glutamatergic neurons, which are the setters of spinal cord excitability and rhythm [3,4]
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Studies have found that V2a neurons participate in the construction of the modular structure of spinal cord movement, and dominate the speed and rhythm of spinal cord movement
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For a long time, whether excitatory V2a interneurons in the spinal cord participate in and determine the escape induced by the hindbrain Mauthner cells has been a key scientific issue in the field
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Recently, Professor Song Jianren of Tongji University, Professor El Manira of Karolinska Institutet, and Researcher Hua Yunfeng of Shanghai Institute of Precision Medicine published a research paper in PNAS: A specialized spinal circuit for command amplification and directionality during escape behavior
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The results of this research confirmed the decision of V2a interneurons to regulate behavior
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In order to answer the above questions, the author of this article conducted the following research using adult zebrafish as a model animal
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First, the researchers discovered a group of acetylcholinergic V2a neurons expressing Chx10 on the transgenic fish line Tol-056 through Patch-seq, electrophysiology and morphology.
Further studies found that they were activated in avoidance behavior and received Mauthner.
The single synaptic signal of the cell comes in
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This result is different from the traditional belief that V2a neurons are only glutamatergic.
It not only confirms the existence of acetylcholinergic V2a neurons but also finds that they are involved in avoidance behavior
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In order to verify the role of this group of neurons in generating neural circuits in escape behavior, the researchers used three-channel whole-cell patch clamp recording, and recorded Mauthner cells, acetylcholinergic V2a (esV2a) neurons, and glycinergic CoLo neurons/ Primary motor neuron
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When Mauthner cells are stimulated to generate action potentials, esV2a neurons, and then CoLo neurons/primary motor neurons are activated
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After killing esV2a neurons with the two-photon laser elimination experiment, Mauthner cells can no longer activate CoLo neurons/primary motor neurons
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The dual-channel whole-cell patch clamp recording study further proves that esV2a neurons can excite CoLo neurons/primary motor neurons through a single synapse, and there is a strong single synaptic connection between esV2a neurons in the spinal cord
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In order to further analyze the connection map between Mauthner cells, esV2a neurons, CoLo neurons and primary motor neurons, the researchers used large-scale three-dimensional electron microscopy reconstruction to perform structural imaging and loop connection analysis of spinal cord segments
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The results showed that the single synapses formed by Mauthner cells and esV2a neurons are chemical synapses and electrical synapses, but they only form electrical synapses with CoLo neurons and primary motor neurons
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The subsequent electrophysiological data further verified the results of the electron microscopy analysis
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The above experiments prove that spinal cord esV2a neurons can further amplify the avoidance commands generated by Mauthner cells in the spinal cord, and work with Mauthner cells to activate CoLo neurons/primary motor neurons to complete the avoidance behavior
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After further two-photon elimination of esV2a neurons in living animals, the animals lose the ability to choose the direction of avoidance response
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The above results prove that there is a neural circuit mechanism in the spinal cord to avoid behavior
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Associate Professor Guan Na of Tongji University and PhD student Xu Lulu of Tongji University are the co-first authors of the paper.
Professor Song Jianren of Tongji University, Professor El Manira of Karolinska Institutet and Researcher Hua Yunfeng of Shanghai Institute of Precision Medicine are the co-corresponding authors of this paper
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This research was guided and supported by researcher Du Jiulin from the Institute of Neuroscience of the Chinese Academy of Sciences, researcher Peng Gang from the Institute of Brain Science of Fudan University, and researcher Peng Changgeng from the Tongji University School of Medicine
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Professor Song Jianren's research group and collaborators from Tongji University have conducted a series of in-depth studies on the role of spinal cord V2a interneurons in motor behavior in recent years
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It was found to be involved in the modular structure and set slow, medium and fast motion rhythms with modular microloops.
The article was published in Neuron in March 2020; to analyze the contribution of V2a interneurons to synaptic transmission by diversified functions , Proving that V2a interneurons have a decisive effect on the production of spinal cord motor rhythm and excitability.
The article was published in Nature Communications in August 2018
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Recruitment Information The Song Jianren research group of Tongji University and the Hua Yunfeng research group of Shanghai Jiaotong University jointly recruit high-paying postdoctoral fellows.
The main research direction is to analyze the function and structure of neural circuits by combining electrophysiology and three-dimensional electron microscopy
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Resume delivery (if interested, please send your resume and other materials to): https://jinshuju.
net/f/ZqXwZt or scan the QR code to submit the original resume link: https:// 42/e2106785118‍ Platemaker: Eleven References 1.
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