Microglia enable cross-modal plasticity by removing inhibitory synapses

Hashimoto, Akinori; Kawamura, Nanami; Tarusawa, Etsuko; Takeda, Ikuko; Aoyama, Yuki; Ohno, Nobuhiko; Inoue, M.; Kagamiuchi, Mai; Kato, Daisuke; Matsumoto, Mami; Hasegawa, Yoshihiro; Nabekura, Junichi; Schaefer, Anne; Moorhouse, Andrew J.; Yagi, T.

doi:10.1016/j.celrep.2023.112383

Cited by 12 publications

(11 citation statements)

References 82 publications

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“…This maybe have prevented us from detecting group differences and making sex- or age-specific observations. Second, our study could not distinguish between microglial subpopulations, which respond to distinct cell types (Hashimoto et al, 2023; Ngozi & Bolton, 2022). For instance, there are microglial subpopulations that specifically respond to inhibitory neurons expressing both Gabbr1 and Gabbr2 , revealing GABA B receptiveness (Favuzzi et al, 2021).…”

Section: Discussionmentioning

confidence: 89%

“…For instance, there are microglial subpopulations that specifically respond to inhibitory neurons expressing both Gabbr1 and Gabbr2 , revealing GABA B receptiveness (Favuzzi et al, 2021). Furthermore, inhibitory synapse editing in the visual cortex is mediated by microglial MMP-9 (Hashimoto et al, 2023). Given that PNNs predominantly surround parvalbumin-expressing inhibitory interneurons, it raises a compelling question: is there a specific link between these microglial subpopulations and the regulation of PNNs surrounding parvalbumin-expressing inhibitory neurons in the vmPFC?…”

Section: Discussionmentioning

confidence: 99%

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Postmortem evidence of microglial involvement in the child abuse-associated increase of perineuronal nets in the ventromedial prefrontal cortex

Belliveau,

Rahimian,

Fakhfouri

et al. 2024

Preprint

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Microglia, versatile in their functions within the central nervous system, have recently been recognized for their capacity to degrade extracellular matrix. Perineuronal nets (PNNs), a specialized form of this matrix, are crucial for stabilizing neuronal connections and constraining plasticity. Our group recently reported increased PNN densities in the ventromedial prefrontal cortex (vmPFC) of adult depressed suicides with a history of child abuse, compared to matched controls. To explore the underlying mechanisms, we used here a comprehensive approach in similar postmortem vmPFC samples, combining a human matrix metalloproteinase array, isolation of CD11b-positive microglia and enzyme-linked immunosorbent assays. Our results indicate a significant downregulation of matrix metalloproteinase (MMP)-9 and tissue inhibitors of metalloproteinases (TIMP)-2 in both whole vmPFC grey matter and isolated microglia. Furthermore, our experiments revealed that a history of child abuse was associated with a dampening of intercellular communication between microglia and neurons through CX3CR1 and IL33R. Taken together, these findings suggest that microglial function is lastingly disrupted in the vmPFC of adults having experienced sever adversity during childhood, thus providing a potential mechanism for the previously reported child abuse-associated PNN alterations.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Postmortem evidence of microglial involvement in the child abuse-associated increase of perineuronal nets in the ventromedial prefrontal cortex

Belliveau,

Rahimian,

Fakhfouri

et al. 2024

Preprint

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“…Additionally, these altered mfALFF and zReHo value may reflect TSD-induced local neuronal injuries ( Luo et al, 2016 ), and enhanced FC with other regions of the brain may represent a compensatory mechanism for such local injuries ( Sheth et al, 2021 ; Hashimoto et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Total sleep deprivation alters spontaneous brain activity in medical staff during routine clinical work: a resting-state functional MR imaging study

Peng,

Guo,

Liu

et al. 2024

Front. Neurosci.

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ObjectivesTo assess the effect of total sleep deprivation (TSD) on spontaneous brain activity in medical staff during routine clinical practice.MethodsA total of 36 medical staff members underwent resting-state functional MRI (rs-fMRI) scans and neuropsychological tests twice, corresponding to rested wakefulness (RW) after normal sleep and 24 h of acute TSD. The rs-fMRI features, including the mean fractional amplitude of low-frequency fluctuation (mfALFF), z-score transformed regional homogeneity (zReHo), and functional connectivity (zFC), were compared between RW and TSD. Correlation coefficients between the change in altered rs-fMRI features and the change in altered scores of neuropsychological tests after TSD were calculated. Receiver operating characteristic (ROC) and logistic regression analyses were performed to evaluate the diagnostic efficacy of significantly altered rs-fMRI features in distinguishing between RW and TSD states.ResultsBrain regions, including right superior temporal gyrus, bilateral postcentral gyrus, left medial superior frontal gyrus, left middle temporal gyrus, right precentral gyrus, and left precuneus, showed significantly enhanced rs-fMRI features (mfALFF, zReHo, zFC) after TSD. Moreover, the changes in altered rs-fMRI features of the right superior temporal gyrus, bilateral postcentral gyrus, left middle temporal gyrus, and left precuneus were significantly correlated with the changes in several altered scores of neuropsychological tests. The combination of mfALFF (bilateral postcentral gyrus) and zFC (left medial superior frontal gyrus and left precuneus) showed the highest area under the curve (0.870) in distinguishing RW from TSD.ConclusionSpontaneous brain activity alterations occurred after TSD in routine clinical practice, which might explain the reduced performances of these participants in neurocognitive tests after TSD. These alterations might be potential imaging biomarkers for assessing the impact of TSD and distinguishing between RW and TSD states.

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“…Synaptic stripping is the physical disruption of synaptic transmission by the insertion of microglial processes between the presynaptic and postsynaptic regions (Trapp et al, 2007). Previous studies have also suggested that microglia strip or phagocytose inhibitory synapses during conditions of health and disease, including during epilepsy (Carrillo et al, 2020;Chen et al, 2014;Hashimoto et al, 2023;Wan et al, 2020;Wittner & Magl oczky, 2017).…”

Section: Microglial Function In the Mgb After Sementioning

confidence: 99%

Microglia induce auditory dysfunction after status epilepticus in mice

Araki,

Hiragi,

Kuga

et al. 2023

Glia

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Auditory dysfunction and increased neuronal activity in the auditory pathways have been reported in patients with temporal lobe epilepsy, but the cellular mechanisms involved are unknown. Here, we report that microglia play a role in the disinhibition of auditory pathways after status epilepticus in mice. We found that neuronal activity in the auditory pathways, including the primary auditory cortex and the medial geniculate body (MGB), was increased and auditory discrimination was impaired after status epilepticus. We further demonstrated that microglia reduced inhibitory synapses on MGB relay neurons over an 8‐week period after status epilepticus, resulting in auditory pathway hyperactivity. In addition, we found that local removal of microglia from the MGB attenuated the increase in c‐Fos+ relay neurons and improved auditory discrimination. These findings reveal that thalamic microglia are involved in auditory dysfunction in epilepsy.

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Microglia enable cross-modal plasticity by removing inhibitory synapses

Cited by 12 publications

References 82 publications

Postmortem evidence of microglial involvement in the child abuse-associated increase of perineuronal nets in the ventromedial prefrontal cortex

Postmortem evidence of microglial involvement in the child abuse-associated increase of perineuronal nets in the ventromedial prefrontal cortex

Total sleep deprivation alters spontaneous brain activity in medical staff during routine clinical work: a resting-state functional MR imaging study

Microglia induce auditory dysfunction after status epilepticus in mice

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