Neurosci Bull︱Shen Ying's team reveals the three-dimensional heterogeneity of projections from the cerebellar nucleus to the thalamus

Written by Ma Kuangyi, edited by Shen Ying, Wang Sizhen’s cerebellum is "small" because it only accounts for 10% of the total brain volume
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In fact, the cerebellum is not "small", it occupies 70% of the number of neurons in the whole brain
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It has long been believed that the main function of the cerebellum is to coordinate movement, but more and more evidence shows that the cerebellum is involved in many non-motor functions, such as cognition, language, and emotion
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These functions mean that the cerebellum is involved in the information processing process of the cortex by dominating the pre-motor center and non-motor-related brain areas
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Therefore, the latest international concept of "cerebellar connectome" co-processing non-motor behavior [1]
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Regardless of sports or non-motor behaviors, the thalamic complex is a key relay area for cerebellar output.
It has many connections with the cerebral cortex, such as the contralateral and/or ipsilateral motor cortex, premotor cortex, entorhinal cortex, prefrontal cortex, auditory cortex, cingulate cortex and the like
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There is evidence that deep cerebellar nuclei (DCN) neurons are connected to multiple nuclei of the thalamus, such as the ventrolateral thalamic nuclei (VL), centrolateral thalamic nuclei (CL), and abdominal Medial thalamic nuclei (ventromedial thalamic nuclei, VM), and further exploration of the spatial distribution of the cerebellar projections on the thalamic nucleus will help to further analyze the motor and non-motor functions of the cerebellum
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 On October 5, 2021, in the latest cover paper of Neuroscience Bulletin entitled "Three-dimensional heterogeneity of cerebellar interposed nucleus-recipient zones in the thalamic nuclei", Kuang-Yi Ma of Zhejiang University , Article 1), Ying Shen (Corresponding author) and others have studied this scientific problem
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The study revealed the three-dimensional spatial heterogeneity of cerebellar IpN-thalamic VL projections, and that IpN only forms a functional connection with the contralateral VL, providing new evidence for understanding the diversified cerebellar influence on the thalamus-cortical network
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 The study selected the cerebellar interposed nucleus (IpN) in the DCN, which is most closely connected to the forebrain, electrically stimulated IpN under anesthesia in mice, and recorded the evoked field potentials of the projection nucleus thalamus VL and CL in vivo (Evoked potential, EP)
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The results show that the functional cerebellar-thalamic projection only exists between the IpN and the contralateral VL: applying different intensities of electrical stimulation to the IpN can record EPs with different response amplitudes in the VL (Figure 1), but not in the CL.

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Fig.
1 Different IpN stimulation intensities can induce VL potentials with different response amplitudes (picture quoted from: Ma et al.
, Neurosci Bull 2021).
During the in vivo recording of EP induced by IpN-VL projections on the downstream nucleus, the author found that Recording at different positions of the nucleus can result in different induced EPs (Figure 2B, C)
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Next, the author's team conducted a statistical analysis of the induced EP in each subregion of the downstream nucleus, and found that IpN-VL projections have previously unknown three-dimensional spatial heterogeneity in the sagittal and coronal planes of the VL nucleus
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The evoked EP amplitude of the number of activated neurons in each subregion was counted.
After normalization, the three-dimensional spatial distribution heterogeneity is shown in Figure 2D and E in the form of heat maps
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Figure 2 The spatial heterogeneity of VL potentials induced by electrical stimulation of IpN (picture quoted from: Ma et al.
, Neurosci Bull 2021) In order to further evaluate the projection intensity of IpN-VL, the author used the transsynaptic virus AAV1.
hSyn.
Cre.
T2A .
eGFP and AAVretro.
CMV.
bClobin.
eGFP respectively performed anterograde and retrograde neural tracing of the targeted neurons projected from IpN to VL (Figure 3)
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Similarly, the results of counting targeted neurons also show that the IpN-VL projections are non-uniformly distributed, and the most concentrated IpN-VL projection area can be observed at the AP-1.
2 coronal plane of the VL nucleus
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Figure 3 Schematic diagram of IpN-VL projection retrograde tracing and neuron statistical results (picture quoted from: Ma et al.
, Neurosci Bull 2021) The author's in-vivo electrophysiological records and virus tracing results all reveal IpN projection neurons The three-dimensional spatial distribution of VL in the thalamus is heterogeneous
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The author then analyzed the correlation between the electrophysiology of IpN-VL projection and the virus tracing data (Figure 4)
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VL sagittal EP amplitude and the number of projection neurons were analyzed by Pearson correlation, and the determinant coefficient between the two variables was calculated, which confirmed the correlation between EP value and the number of projection neurons; VL The analysis of the coronal level also proves that the electrophysiology of IpN-VL projection at this level is significantly correlated with the virus tracing data
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Figure 4 Correlation analysis between the EP amplitude of IpN-VL projection and the number of neurons in different sub-regions of VL (picture quoted from: Ma et al.
, Neurosci Bull 2021) Figure 5 Work summary drawing: three-dimensional projection of IpN-VL Spatial heterogeneity (picture quoted from: Ma et al.
, Neurosci Bull 2021) Conclusion and discussion of the article, inspiration and prospects To sum up, the study used in vivo electrophysiological recording and trans-synaptic virus tracing experiments The method revealed the three-dimensional spatial heterogeneity of the cerebellar IpN-thalamic VL projection (Figure 5), and IpN only forms a functional connection with the contralateral VL
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This study provides evidence for understanding the diversified influence of the cerebellum on the thalamic cortical network, and further reveals the structure of the cerebellum-thalamus-cerebral cortex circuit from both functional and structural aspects
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It is of great significance for understanding cerebellar-related motor and non-motor diseases .

 At present, one of the focuses of global brain science is how to connect and participate in various behaviors and related diseases
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In September 2021, the Ministry of Science and Technology of China promulgated the "China Brain Project".
One of the important tasks is to draw a complete and detailed brain connection map
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An fascinating technique is to perform large-scale continuous fluorescence tracking and in vivo imaging at subcellular resolution.
For this reason, Chinese scientists invented fluorescence microscopy optical slice tomography (fMOST) [2], which is used in many laboratories And published a high-level paper
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While this technology clarifies the connections between various brain areas from a morphological point of view, research is needed to prove that these connections are functional
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Just as patch-clamp electrophysiological recording has always been an important manifestation of neuronal function, exploring and verifying the three-dimensional spatial distribution of brain projections in somatic neuroelectrophysiological recording will clarify brain connections from a functional perspective
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In this sense, the work of Professor Shen Ying's team provides a new direction for thinking in this field
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Future research will need to combine fMOST and electrophysiological recording to obtain a complete three-dimensional functional map projected from each brain area of ​​the brain
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Original link: https://link.
springer.
com/article/10.
1007/s12264-021-00780-y First author Ma Kuangyi (second row, first right), second author Cai Xinyu (fourth row, second right), corresponding author Shen Ying (middle of the front row)
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(Photo provided from: Shen Ying Laboratory) Ma Kuangyi and Shen Ying completed the overall design research, Ma Kuangyi, Cai Xinyu, Wang Xintai, Wang Zhaoxiang, etc.
completed the research, Ma Kuangyi, Feng Zhouyan, and Shen Ying completed the data analysis, Ma Kuangyi , Feng Zhouyan and Shen Ying finished writing
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The research was funded by the National Outstanding Youth Project of the National Foundation of China, key international cooperation projects, general projects, and key research and development projects of the Ministry of Science and Technology
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Shen Ying, National Outstanding Youth, Qiushi Distinguished Professor of Zhejiang University, New Century Outstanding Talent of the Ministry of Education
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Presided over the 973 project, the national key research and development plan, the national major scientific research plan, the National Natural Science Foundation of China, and the Zhejiang Natural Science Foundation talents/key projects, and discovered many important molecules and mechanisms that affect the transmission, integration and function of neuroinformation.
Communication Published papers with the first author in Nat Neurosci, Neuron, PNAS, J Neurosci, etc.
, and is the editor of Front Cell Neurosci, Sci Rep, Cerebellum, ACN Neuro and Neurochem Int
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For long-term recruitment of postdoctoral fellows in the laboratory, please contact yshen@zju.
edu.
cn
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Selected articles from previous issues [1] J Neurosci︱ Junli Cao’s research group reveals the loop mechanism of anterior cingulate gyrus to regulate mirror pain [2] Nat Commun︱ non-human primate (monkey marmoset) autism model reveals early human disease Developmental biological abnormalities [3] Cell Discovery︱ Ma Yuanwu/Shen Bin’s team achieved the first accurate editing of rat mitochondrial DNA [4] Dev Cell︱ Lactic acid promotes peripheral nerve damage and repair B side: Long-term axon lactate metabolism will increase Oxidative stress and axon degeneration [5] Nat Commun︱ selective inhibition of microglia activation is expected to alleviate pathological α-syn transmission [6] Does Science︱ serotonin help overcome cocaine addiction? [7] Mol Psychiatry︱ Gao Tianming’s research group reveals the different roles of astrocytes and neurons in synaptic plasticity and memory [9] Sci Transl Med︱ Xiang Xianyuan and others reveal the brain’s immune cells crazy sugar phagocytosis, helping nerves Early diagnosis of degenerative diseases [9] A new mechanism of Mol Cell︱ Alzheimer's disease: Tau protein oligomerization induces nuclear cell transport of RNA binding protein HNRNPA2B1 and mediates enhancement of m6A-RNA modification [10] Cereb Cortex | Li Tao project The group reported the abnormality of the cortical myelin covariation network with the deep characteristics of the cerebral cortex in schizophrenia [11] Cell︱ hold hands, advance and retreat together! Microglia form a cell-connected network and work together to degrade pathological α-syn.
Recommended high-quality scientific research training courses [1] Data map life-saving guide! How good is it to learn these software? 【2】JAMA Neurol︱Attention! Young people are more likely to suffer from "Alzheimer's disease"? [3] Patch clamp and optogenetics and calcium imaging technology seminar (October 30-31) References (slide up and down to view) [1] Sathyanesan A, Zhou J, Scafidi J, Heck DH, Sillitoe RV, Gallo V .
Emerging connections between cerebellar development, behaviour and complex brain disorders.
Nat Rev Neurosci 2019, 20: 298-313.
[2] Li A, Gong H, Zhang B, Wang Q,