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    Home > Active Ingredient News > Study of Nervous System > Nature Sub-Journal: Professor Yin Dongmin from East China Normal University reveals that dopamine receptors regulate synaptic pruning

    Nature Sub-Journal: Professor Yin Dongmin from East China Normal University reveals that dopamine receptors regulate synaptic pruning

    • Last Update: 2021-12-07
    • Source: Internet
    • Author: User
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    During the developmental period, the functional synapses are further strengthened and stabilized, and the unnecessary or weak synapses are eliminated
    .

    Normal synaptic pruning is essential for establishing correct synaptic connections, while abnormal synaptic pruning can cause schizophrenia, anxiety, autism and other diseases
    .

    There are two types of dopamine receptors in the brain: excitatory D1-like receptors (Drd1 and Drd5) and inhibitory D2-like receptors (Drd2, Drd3, and Drd4)
    .

    Among them, Drd2 allele mutations cause a decrease in the expression of Drd2 in the brain, which is related to anxiety and depression
    .

    Drd2 is mainly expressed at the synaptic ends of dopamine neurons and regulates the release of dopamine
    .

    On November 8, 2021, Dongmin Yin's group from the School of Life Sciences, East China Normal University discovered that dopamine Drd2 regulates synaptic pruning through a cell-autonomous mechanism that activates mTOR signaling.
    Abnormal synaptic pruning in adolescence can cause anxiety-like behavior
    .

    Immunofluorescence experiments found that the neurons expressing Drd2 in the anterior cingulate cortex (ACC) brain area were mainly located in the fifth layer.
    Based on this anatomical feature, this area became the research target area
    .

    The researchers found that during normal development, the number of Drd2-positive neurons increased in the number of dendritic spines from the 2nd to the 4th week, and the number of dendritic spines gradually decreased after the 8th week
    .

    The dendritic spine density changes of different age groups did not decrease in the number of dendritic spine after the 8th week in the Drd2 knockdown rats, and the number of the dendritic spine from the 2nd week to the 4th week was similar to that of normal mice.
    Impairment of contact pruning, but does not affect the formation of synapses during development
    .

    Electrophysiological experiments found that the tiny excitatory postsynaptic current (mEPSC) of 4-week-old Drd2 knockdown rats was normal, but the frequency of mEPSC increased after 5 weeks of age, which was consistent with the above-mentioned dendritic spine morphology results
    .

    After continuous injection of Drd2 antagonist into the ACC brain area of ​​3-week-old rats (before the disappearance of the synapses), the dendritic spine density of neurons increased at the 5th week, excitatory postsynaptic currents increased, and inhibitory synapses There is no change in current, and glutamatergic transmission is enhanced, which is consistent with the result caused by gene knockdown of Drd2
    .

    These results indicate that Drd2 regulates synaptic pruning during a critical period of development (puberty)
    .

    Previous studies have shown that the down-regulation of Drd2 causes the activation of the AKT/mTOR signaling pathway
    .

    The activation of mTOR signaling pathway is involved in synaptic pruning disorders in autism
    .

    Molecular biology experiments show that the AKT/mTOR signaling pathway in the ACC brain area of ​​Drd2 knockdown rats is activated.
    After 8 weeks of injection of mTOR inhibitors into this brain area, the dendritic spine density of the neurons of Drd2 knockdown rats decreases, and the frequency of mEPSC Reduce to normal levels
    .

    This indicates that mTOR signaling mediates synaptic pruning dysfunction caused by Drd2 knockdown
    .

    Specific injection of Drd2 antagonist into the ACC brain area of ​​3-4 weeks old rats caused anxiety-like behavior in rats, but did not cause social behavior disorder, and injection of Drd2 antagonist in 8-week-old rats did not cause anxiety-like behavior Behavior, which indicates that the decreased expression of Drd2 in adolescence causes abnormal synaptic pruning, and finally induces anxiety-like behavior
    .

    In general, the adolescent ACC brain area Drd2 mediated synaptic pruning dysfunction leads to enhanced glutamate transmission and induces anxiety-like behaviors
    .

    [References]|https://doi.
    org/10.
    1038/s41467-021-26769-9 The pictures in the text are from the references 
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