Transcriptional corepressor SIN3A regulates hippocampal synaptic plasticity via Homer1/mGluR5 signaling

Bridi, Morgan S.; Schoch, Hannah; Florian, Cédrick; Poplawski, Shane G.; Banerjee, Anamika; Hawk, Joshua D.; Porcari, Giulia S.; Lejards, Camille; Hahn, Chang-Gyu; Giese, K. Peter; Havekes, Robbert; Spruston, Nelson; Abel, Ted

doi:10.1172/jci.insight.92385

Cited by 23 publications

(14 citation statements)

References 79 publications

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“…In the mouse, conditional knockout of Sin3a in forebrain excitatory neurons results in a small yet reproducible (20–25%) increase in expression of Homer1 and cyclin‐dependent kinase Cdk5 , two genes encoding factors involved in memory consolidation, associated with an increase in hippocampal activity. [ 62 ]…”

Section: Global Regulation Through Soft Repressionmentioning

confidence: 99%

Soft repression: Subtle transcriptional regulation with global impact

et al. 2020

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Pleiotropically acting eukaryotic corepressors such as retinoblastoma and SIN3 have been found to physically interact with many widely expressed “housekeeping” genes. Evidence suggests that their roles at these loci are not to provide binary on/off switches, as is observed at many highly cell‐type specific genes, but rather to serve as governors, directly modulating expression within certain bounds, while not shutting down gene expression. This sort of regulation is challenging to study, as the differential expression levels can be small. We hypothesize that depending on context, corepressors mediate “soft repression,” attenuating expression in a less dramatic but physiologically appropriate manner. Emerging data indicate that such regulation is a pervasive characteristic of most eukaryotic systems, and may reflect the mechanistic differences between repressor action at promoter and enhancer locations. Soft repression may represent an essential component of the cybernetic systems underlying metabolic adaptations, enabling modest but critical adjustments on a continual basis.

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Section: Global Regulation Through Soft Repressionmentioning

confidence: 99%

Soft repression: Subtle transcriptional regulation with global impact

et al. 2020

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“…The loss of mitochondrial complex I might decrease ATP generation, cause mitochondrial dysfunction and affect the proper function of synapses. Homer protein homolog 1 (Homer1) is a postsynaptic density scaffolding protein and may be involved in synaptic plasticity and development ( Bridi et al, 2020 ). The downregulation of Homer1 indicated that the integrity and function of synapses might be disrupted.…”

Section: Discussionmentioning

confidence: 99%

Confinement induces oxidative damage and synaptic dysfunction in mice

Wang²,

Xin³

et al. 2022

Front. Physiol.

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A confined environment is an enclosed area where entry or exit is highly restricted, which is a risk factor for a work crew’s mental health. Previous studies have shown that a crew is more susceptible to developing anxiety or depression in a confined environment. However, the underlying mechanism by which negative emotion is induced by confinement is not fully understood. Hence, in this study, mice were retained in a tube to simulate short-term confinement. The mice exhibited depressive-like behavior. Additionally, the levels of H2O2 and malondialdehyde in the prefrontal cortex were significantly increased in the confinement group. Furthermore, a label-free quantitative proteomic strategy was applied to analyze the abundance of proteins in the prefrontal cortex of mice. A total of 71 proteins were considered differentially abundant proteins among 3,023 identified proteins. Two differentially abundant proteins, superoxide dismutase [Mn] and syntaxin-1A, were also validated by a parallel reaction monitoring assay. Strikingly, the differentially abundant proteins were highly enriched in the respiratory chain, oxidative phosphorylation, and the synaptic vesicle cycle, which might lead to oxidative damage and synaptic dysfunction. The results of this study provide valuable information to better understand the mechanisms of depressive-like behavior induced by confined environments.

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“…The interaction of Homer and Shank, two proteins of the postsynaptic density (PSD), result in morphological changes in dendritic spines [ 161 ] and to an association of group I mGlu receptors with the NMDAR signaling pathway [ 162 , 163 ]. Furthermore, increased levels of mGlu5 receptors and Homer1 proteins in Sin3aNH transgenic mice result in enhanced hippocampus-dependent memory and synaptic plasticity [ 164 ]. Another element in the mGlu5 receptor mediation of synaptic plasticity involves their interaction with PSD-95/Disk large/ZO-1 (PDZ) domains [ 165 ].…”

Section: Contribution Of Mglu5 To Persistent Forms Of Hippocampal Syn...mentioning

confidence: 99%

Role of mGlu5 in Persistent Forms of Hippocampal Synaptic Plasticity and the Encoding of Spatial Experience

Hagena

Manahan‐Vaughan

2022

Cells

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The metabotropic glutamate (mGlu) receptor family consists of group I receptors (mGlu1 and mGlu5) that are positively coupled to phospholipase-C and group II (mGlu2 and mGlu3) and III receptors (mGlu4-8) that are negatively coupled to adenylyl cyclase. Of these, mGlu5 has emerged as a key factor in the induction and maintenance of persistent (> 24 h) forms of hippocampal synaptic plasticity. Studies in freely behaving rodents have revealed that mGlu5 plays a pivotal role in the stabilisation of hippocampal long-term potentiation (LTP) and long-term depression (LTD) that are tightly associated with the acquisition and retention of knowledge about spatial experience. In this review article we shall address the state of the art in terms of the role of mGlu5 in forms of hippocampal synaptic plasticity related to experience-dependent information storage and present evidence that normal mGlu5 function is central to these processes.

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Transcriptional corepressor SIN3A regulates hippocampal synaptic plasticity via Homer1/mGluR5 signaling

Cited by 23 publications

References 79 publications

Soft repression: Subtle transcriptional regulation with global impact

Soft repression: Subtle transcriptional regulation with global impact

Confinement induces oxidative damage and synaptic dysfunction in mice

Role of mGlu5 in Persistent Forms of Hippocampal Synaptic Plasticity and the Encoding of Spatial Experience

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