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    Home > Active Ingredient News > Study of Nervous System > What makes Cell "defend the territory"?

    What makes Cell "defend the territory"?

    • Last Update: 2022-03-09
    • Source: Internet
    • Author: User
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    By | Qi In nature, male lions are often quick to identify the gender of a "stranger" who invades their territory, and if the intruder is also a male, they will attack immediately, while if it is a female, they will usually be polite.
    courtship behavior
    .

    In contrast, lioness companions display maternal brilliance rather than territorial aggression, and they primarily attack any target that threatens their cubs
    .

    After millions of years of evolution, this typically sex-dependent social behavior has been integrated into animal brains
    .

    Sex hormones have profound effects on sex-dependent behavior, and neurons in the bed nucleus of stria terminalis (BNSTpr), medial amygdala (MeA), preoptic hypothalamus (POA), and ventromedial ventrolateral hypothalamus (VMHvl) have been identified.
    have been shown to regulate sex- or estrous-state-dependent mating and aggression performance [1-4], and while studies of these regions have uncovered many transcriptome-defined cell types, sex- or estrous-state-dependent differentially expressed genes are not known Rarely [5, 6]
    .

    On January 21, 2022, the team of Nirao M.
    Shah from Stanford University published an article entitled A functional cellular framework for sex and estrous cycle-dependent gene expression and behavior in the journal Cell.
    , POA and VMHvl, four structures expressing estrogen receptor 1 (Esr1+), were subjected to scRNA-seq and ribosome affinity purification (TRAP-seq), and 1415 estrogen receptor 1 (Esr1+) structures were identified.
    differentially expressed genes
    .

    By marking the differentially expressed genes of individual Esr1+ cell types as entry points, the researchers found that two cell types, BNSTprTac1/Esr1 and VMHvlCckar/Esr1, are essential for sex recognition in males and mating behavior in females
    .

    Taken together, this study demonstrates the presence of a multitude of different sex- and estrous state-dependent cell types in the mammalian brain whose projections and functional specialization enable sex hormone-responsive populations to modulate distinct social behaviors
    .

    Adult males maintain testosterone in a steady state and reliably initiate sex-hormone-dependent social behavior, while females exhibit cyclical changes in sex-hormone titers, with peak titers during estrus opening a window of sexual receptivity
    .

    Because such cyclical changes may confound the identification of DEGs, we constructed estrus receptive females (FR) and relative interestrous nonreceptive females (FNR) with estrogen and progesterone priming.
    )
    .

    We performed TRAP-seq on BNSTpr, MeA, POA and VMHvl from adult FR, FNR and gonadal intact male mice (M) and identified a total of 1541 differentially expressed genes (sDEGs) associated with sex, as well as estrus Status-related 770 differentially expressed genes (eDEGs)
    .

    Due to the overlap between the two groups, we ended up with 1415 genes that were differentially expressed between sexes or estrus states
    .

    Gene ontology analysis revealed that these DEGs were significantly enriched in synaptic transmission, steroid hormone-related pathways, peripheral reproductive organ pathways, etc.
    , while disease ontology analysis revealed enrichment associated with multiple gender-biased disorders, such as autism Syndrome Spectrum Disorders
    .

    Next, the researchers examined the distribution of DEGs in different Esr1+ populations by in situ hybridization (ISH), and the extensive or restricted expression of different genes in different populations indicated that the cell types in these four Esr1+ populations were comparable.
    large heterogeneity
    .

    To this end, we used snRNA-seq of four structures of Esr1+ neurons in three groups of mice to characterize the distribution of DEGs at single-cell resolution and attempt to determine the behavioral role of individual cell types relative to other Esr1+ cell types in the population
    .

    They found that BNSTprTac1/Esr1 cell types in the BNSTprEsr1 population were significantly upregulated in M ​​compared to FR and FNR, and then they inhibited BNSTprTac1/Esr1 neurons by delivering AAV-flex-DREADDi:mCherry to adult male Tac1Cre mice Activity, in the sniff test, this treatment resulted in a loss of sex judgment in males, whereas suppression of the remaining BNSTprTac1-/Esr1 cell population did not disrupt urine preference
    .

    Therefore, the researchers reasoned that this type of neuron is essential for gender recognition, mating with females, and aggression toward males only in males
    .

    VMHvlCckar/Esr1 is highly enriched in FR mice, and Cckar signaling is known to regulate female mating, and inhibition of Cckar results in poor female mating [7]
    .

    Based on this, the researchers wanted to know the contribution of VMHvlCckar+/Esr1 or the rest of VMHvlCckar-/Esr1 cells to female mating and other social interactions
    .

    Chemogenetic inhibition of the VMHvlCckar+/Esr1 cell type significantly suppressed sexual behavior in CckarCre FR mice, with an 8-fold reduction in the dorsiflexion posture used by females to achieve mating, and increased rejection of the opposite sex
    .

    Suppression of CckarCre FR mice during lactation did not affect the performance of "bring the baby back to the nest", and inhibition of the remaining VMHvlCckar-/Esr1 cells affected the maternal performance, indicating that VMHvlCckar+/Esr1 or the remaining VMHvlCckar- /Esr1 cells regulate female mouse sexual behavior and maternal performance in a complementary manner, respectively
    .

    It has been previously reported that the projection of VMHvlEsr1 neurons to the hypothalamic anterior ventral periventricular nucleus (AVPV) is critical for mating in FR mice [8], so do the previously identified VMHvlCckar+/Esr1 cells preferentially project into the AVPV? The researchers delivered a Cre-dependent synaptophysin:mCherry (Syp:mCherry) adeno-associated virus that marks the presynaptic terminal to the VMHvl of CckarCre female mice, or a virus that is expressed only in Cckar-deficient cells
    .

    More mCherry was observed in the AVPV of the Cckar+ group, however this projection was >10-fold reduced in male mice, consistent with previous reports that the projection of VMHvlEsr1 neurons to the AVPV is dimorphic
    .

    Collectively, this study identifies differentially expressed genes in four Esr1+-expressing populations in different sexes or estrus states, as well as functional signatures of specific cell types that mediate social behavior in male or female mice
    .

    Prof.
    Nirao M.
    Shah, corresponding author of the paper, likens the work done by his team to "finding a needle in a haystack," saying that "cells critical to the performance of typical gender recognition, dating, mating, or hateful behavior may account for Less than 0.
    0005% of all cells in the mouse brain
    .

    The 'first needle' is a population of estrogen-responsive cells in these four tiny structures in the mouse brain, and those that regulate gender recognition in males, and those in females, respectively Specific BNST and VMH cell types for sexual receptivity are a 'needle in a needle' in a haystack
    .

    Of course, it remains to be seen what tasks each of the other 35 sex hormone-responsive cell types in the BNST and the other 26 equivalent cell types in the VMH are performing in addition to the two cell types already identified in this study is a mystery
    .

    "Original link: https://doi.
    org/10.
    1016/j.
    cell.
    2021.
    12.
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    Esr1+ cells in the ventromedial hypothalamus control female aggression.
    Nat.
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    -W.
    , and Anderson, DJ (2014).
    Antagonistic control of social versus repetitive self-grooming behaviors by separable amygdala neuronal subsets.
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    Nature 589, 258–263.
    5.
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    , Huang, S.
    , Micevych, PE, and Hong, W.
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    Sexually Dimorphic Control of Parenting Behavior by the Medial Amygdala.
    Cell 176, 1206–1221.
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    , Yao, Z.
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    , Yi, L.
    , Koulena, N.
    , Pierson, N.
    , et al.
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    Multimodal Analysis of Cell Types in a Hypothalamic Node Controlling Social Behavior.
    Cell 179, 713–728.
    e17.
    7.
    Micevych, P.
    , and Sinchak, K.
    (2001).
    Estrogen and endogenous opioids regulate CCK in reproductive circuits.
    Peptides 22, 1235–1244.
    8.
    Inoue, S.
    , Yang, R.
    , Tantry, A.
    , Davis, C.
    -H.
    , Yang, T.
    , Knoedler, JR, Wei, Y.
    , Adams, EL, Thombare, S.
    , Golf, SR, et al.
    (2019).
    Periodic Remodeling in a Neural Circuit Governs Timing of Female Sexual Behavior.
    Cell 179, 1393– 1408.
    e16.
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