Microglia Enhance Synapse Activity to Promote Local Network Synchronization

Akiyoshi, Ryohei; Wake, Hiroaki; Kato, Daisuke; Horiuchi, Hiroshi; Ono, Riho; Ikegami, Ako; Haruwaka, Koichiro; Omori, Toshiaki; Tachibana, Yoshihisa; Moorhouse, Andrew J.; Nabekura, Junichi

doi:10.1523/eneuro.0088-18.2018

Cited by 135 publications

(130 citation statements)

References 33 publications

(53 reference statements)

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“…Moreover, microglial contact lowered activity of targeted neuron, indicating that they are regulating neural activity by making interaction with processes. The opposite effect has also been seen where microglial contact with spines induces calcium activity in that postsynaptic site . These findings indicate that microglia and neurons communicate bi‐directionally, and thus microglia are not only attracted by neurons, but are also able to affect neural activities.…”

Section: Microglial Machinery Senses Target Synapsesmentioning

confidence: 93%

“…The opposite effect has also been seen where microglial contact with spines induces calcium activity in that postsynaptic site. 49 These findings indicate that microglia and neurons communicate bidirectionally, and thus microglia are not only attracted by neurons, but are also able to affect neural activities. This intricately controlled system underlies brain homeostasis, cognition, learning, and memory.…”

Section: Microglial Machinery Senses Target Synapsesmentioning

confidence: 94%

“…Microglia support synchronized activity of neurons, which is required for proper operation of neural circuits by promoting firing in process‐contacted spines in the healthy brain. Thus, inflammation disturbs the proper condition and plasticity of neural circuits . This indicates that THIK‐1 deficiency in microglia is the new hallmark of several neurodegenerative diseases that are accompanied by inflammation.…”

Section: How Microglial Activation Leads To Impaired Cognitive Functionmentioning

confidence: 99%

“…Taken together, these findings may suggest why microglia surveying occurs in our brains without any major remodeling of synapses. To avoid circuit breakdown or neural death caused by aberrant connections and hyperactivity of synapses, microglial processes need to detect dysregulation of synapses and correct these, as contact can adjust synaptic activities …”

Section: Neuronal Plasticity Excitotoxity and Never‐resting Microgliamentioning

confidence: 99%

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Microglia: Lifelong modulator of neural circuits

Ikegami

Haruwaka

2019

Neuropathology

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Microglia, the sole immune cells in the brain, are the key player for synaptic regulation required for our brain function in both developing and adult brain. They have highly motile processes to detect synaptic functions. Recent accumulated studies have unveiled the mechanism underlying synapse detection and pruning / formation by microglia. In this review, we summarize the current knowledge of various microglial machinery recruited in synaptic modulation in the different life stages and contexts.

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Section: Microglial Machinery Senses Target Synapsesmentioning

confidence: 93%

Section: Microglial Machinery Senses Target Synapsesmentioning

confidence: 94%

Section: How Microglial Activation Leads To Impaired Cognitive Functionmentioning

confidence: 99%

Section: Neuronal Plasticity Excitotoxity and Never‐resting Microgliamentioning

confidence: 99%

See 2 more Smart Citations

Microglia: Lifelong modulator of neural circuits

Ikegami

Haruwaka

2019

Neuropathology

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“…Nevertheless, malfunctioning microglia have the potential to cause damage, such as connectivity problems and impaired myelination, which might result in behavioral changes (Akiyoshi et al, ; Bennett & Barres, ). As already noted, a reduction in TREM2 protein was observed in postmortem brains of autistic subjects (Filipello et al, ), and increased connectivity was detected in Trem2 −/− mice (Filipello et al, ).…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

Microglia roles in synaptic plasticity and myelination in homeostatic conditions and neurodevelopmental disorders

Bar

Barak

2019

Glia

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Microglia are the immune cells of the brain, involved in synapse formation, circuit sculpting, myelination, plasticity, and cognition. Being active players during early development as well as in adulthood, microglia affect other cells directly by their long processes and unique receptors and indirectly by secreting growth factors and cytokines. In this review, we discuss the roles of microglia in neurodevelopmental disorders, synaptic plasticity, myelination, and homeostatic conditions throughout human and mouse development. Within these processes, we specifically focus on the contribution of altered microglial interactions with neurons and oligodendrocytes, altered cytokine and growth factor activities, and alterations in the complement system. We conclude by highlighting future perspectives and providing an overview of future research on microglia.

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Role of chronic neuroinflammation in neuroplasticity and cognitive function: A hypothesis

Lecca

Jung

Scerba

et al. 2022

Alzheimer's & Dementia

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Objective Evaluating the efficacy of 3,6’‐dithioPomalidomide in 5xFAD Alzheimer's disease (AD) mice to test the hypothesis that neuroinflammation is directly involved in the development of synaptic/neuronal loss and cognitive decline. Background Amyloid‐β (Aβ) or tau‐focused clinical trials have proved unsuccessful in mitigating AD‐associated cognitive impairment. Identification of new drug targets is needed. Neuroinflammation is a therapeutic target in neurodegenerative disorders, and TNF‐α a pivotal neuroinflammatory driver. New hypothesis AD‐associated chronic neuroinflammation directly drives progressive synaptic/neuronal loss and cognitive decline. Pharmacologically mitigating microglial/astrocyte activation without altering Aβ generation will define the role of neuroinflammation in AD progression. Major challenges Difficulty of TNF‐α‐lowering compounds reaching brain, and identification of a therapeutic‐time window to preserve the beneficial role of neuroinflammatory processes. Linkage to other major theories Microglia/astroglia are heavily implicated in maintenance of synaptic plasticity/function in healthy brain and are disrupted by Aβ. Mitigation of chronic gliosis can restore synaptic homeostasis/cognitive function.

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Microglia Enhance Synapse Activity to Promote Local Network Synchronization

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Cited by 135 publications

References 33 publications

Microglia: Lifelong modulator of neural circuits

Microglia: Lifelong modulator of neural circuits

Microglia roles in synaptic plasticity and myelination in homeostatic conditions and neurodevelopmental disorders

Role of chronic neuroinflammation in neuroplasticity and cognitive function: A hypothesis

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