Microglia-triggered hypoexcitability plasticity of pyramidal neurons in the rat medial prefrontal cortex

Yamawaki, Yoshio; Wada, Yayoi; Matsui, Sho; Ohtsuki, Gen

doi:10.1016/j.crneur.2022.100028

Cited by 12 publications

(21 citation statements)

References 111 publications

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“…Therefore, brain immunity is the triggering factor of synaptic plasticity via immune receptors, such as pattern-recognition receptors and cytokine receptors, expressed in the neurons. In contrast, activated microglia also modulate the non-synaptic membrane excitability of neurons in the neocortex, hippocampus, amygdala, and cerebellum (Gao et al, 2014 ; Klapal et al, 2016 ; Tzour et al, 2017 ; Duan et al, 2018 ; Luo et al, 2019 ; Yamamoto et al, 2019 ; Zheng et al, 2021 ; Yamawaki et al, 2022 ). In a study by Zhang et al ( 2014 ), changes in waveforms of field EPSPs after microglia activation by exposure to LPS were shown, and the result not only indicated the long-term depression (LTD) of the synaptic transmission but also implied the modulation of the late component of evoked synaptic transmission as an ion-channel modulation.…”

Section: Microglia Heterogeneity and Roles For Modulating Activity Of...mentioning

confidence: 99%

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Immune-Triggered Forms of Plasticity Across Brain Regions

Hikosaka

Kawano

Wada

et al. 2022

Front. Cell. Neurosci.

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Immune cells play numerous roles in the host defense against the invasion of microorganisms and pathogens, which induces the release of inflammatory mediators (e.g., cytokines and chemokines). In the CNS, microglia is the major resident immune cell. Recent efforts have revealed the diversity of the cell types and the heterogeneity of their functions. The refinement of the synapse structure was a hallmark feature of the microglia, while they are also involved in the myelination and capillary dynamics. Another promising feature is the modulation of the synaptic transmission as synaptic plasticity and the intrinsic excitability of neurons as non-synaptic plasticity. Those modulations of physiological properties of neurons are considered induced by both transient and chronic exposures to inflammatory mediators, which cause behavioral disorders seen in mental illness. It is plausible for astrocytes and pericytes other than microglia and macrophage to induce the immune-triggered plasticity of neurons. However, current understanding has yet achieved to unveil what inflammatory mediators from what immune cells or glia induce a form of plasticity modulating pre-, post-synaptic functions and intrinsic excitability of neurons. It is still unclear what ion channels and intracellular signaling of what types of neurons in which brain regions of the CNS are involved. In this review, we introduce the ubiquitous modulation of the synaptic efficacy and the intrinsic excitability across the brain by immune cells and related inflammatory cytokines with the mechanism for induction. Specifically, we compare neuro-modulation mechanisms by microglia of the intrinsic excitability of cerebellar Purkinje neurons with cerebral pyramidal neurons, stressing the inverted directionality of the plasticity. We also discuss the suppression and augmentation of the extent of plasticity by inflammatory mediators, as the meta-plasticity by immunity. Lastly, we sum up forms of immune-triggered plasticity in the different brain regions with disease relevance. Together, brain immunity influences our cognition, sense, memory, and behavior via immune-triggered plasticity.

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Section: Microglia Heterogeneity and Roles For Modulating Activity Of...mentioning

confidence: 99%

“…Subsequently, the intrinsic excitability of L5 pyramidal cells is reduced long-lastingly. In addition, the frequency of spontaneous IPSC decreases, whereas the spontaneous EPSC does not change (Yamawaki et al, 2022 ).…”

Section: Immune-triggered Plasticity In the Cerebellummentioning

confidence: 99%

Immune-Triggered Forms of Plasticity Across Brain Regions

Hikosaka

Kawano

Wada

et al. 2022

Front. Cell. Neurosci.

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“…However, the transient exposure to PGN does not change the neuronal activity in cerebellar neurons [30]. LPS, an endotoxin, is the outer component of Gram-negative bacteria and activates innate inflammation via the patter-recognition receptors (i.e., Toll-like receptors (TLRs)), which drive the invasion into the brain [29][30][31]. Activation of TLR4 on the immune-cell surface results in the activation of hundreds of inflammatory transcriptomes, including pro-inflammatory cytokines such as TNF-α, IL-6, and pro-IL-1β [137].…”

Section: Bacterial Infectionsmentioning

confidence: 99%

“…It is noteworthy that all the inflammatory responses are not always via the translation of genes. Macrophages secrete TNF-α rapidly upon their activation through the non-constitutive pathway [138], which triggers the plasticity of neurons without gene expression [30,31]. TNF-α, IL-1β, and IL-6 are induced and amplified by microglia following the stimulation by LPS, while c-Jun N-terminal kinase (JNK)/p38, external signal-regulated kinase (ERK)/JNK, and ERK/JNK/p38 are involved in their induction, respectively.…”

Section: Bacterial Infectionsmentioning

confidence: 99%

“…In a recent model of acute inflammation in the cerebellar cortex, rodents showed multiple depressive-like behaviors associated with hyperexcitability of Purkinje cells [30]. Transient exposure to lipopolysaccharide (LPS: an outer component of Gram-negative bacteria) of the brain regions and activated microglia induced prominent modulation of synaptic and non-synaptic activity across various types of neurons in the cerebellum, neocortex, hippocampus, striatum, and spinal cord [30][31][32][33][34][35][36][37] (Figure 1A), which may disrupt behaviors and cause disease-like symptoms. In the cerebellar Purkinje cells, acute inflammation by LPS or heat-killed Gram-negative bacteria induces hyperexcitability through akin signaling of the intrinsic plasticity.…”

Section: Introductionmentioning

confidence: 99%

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Acute Cerebellar Inflammation and Related Ataxia: Mechanisms and Pathophysiology

Parvez

Ohtsuki

2022

Brain Sciences

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The cerebellum governs motor coordination and motor learning. Infection with external microorganisms, such as viruses, bacteria, and fungi, induces the release and production of inflammatory mediators, which drive acute cerebellar inflammation. The clinical observation of acute cerebellitis is associated with the emergence of cerebellar ataxia. In our animal model of the acute inflammation of the cerebellar cortex, animals did not show any ataxia but hyperexcitability in the cerebellar cortex and depression-like behaviors. In contrast, animal models with neurodegeneration of the cerebellar Purkinje cells and hypoexcitability of the neurons show cerebellar ataxia. The suppression of the Ca2+-activated K+ channels in vivo is associated with a type of ataxia. Therefore, there is a gap in our interpretation between the very early phase of cerebellar inflammation and the emergence of cerebellar ataxia. In this review, we discuss the hypothesized scenario concerning the emergence of cerebellar ataxia. First, compared with genetically induced cerebellar ataxias, we introduce infection and inflammation in the cerebellum via aberrant immunity and glial responses. Especially, we focus on infections with cytomegalovirus, influenza virus, dengue virus, and SARS-CoV-2, potential relevance to mitochondrial DNA, and autoimmunity in infection. Second, we review neurophysiological modulation (intrinsic excitability, excitatory, and inhibitory synaptic transmission) by inflammatory mediators and aberrant immunity. Next, we discuss the cerebellar circuit dysfunction (presumably, via maintaining the homeostatic property). Lastly, we propose the mechanism of the cerebellar ataxia and possible treatments for the ataxia in the cerebellar inflammation.

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Transcranial NIR Neuromodulation via Multifunctional Nano‐Optical Electrodes for Relieving Depressive Symptoms

Nie,

Zhang,

Wang

et al. 2024

Adv Funct Materials

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Neuromodulation stands as a cornerstone in the therapeutic landscape for neurological disorders, yet the quest for selective stimulation of specific brain regions with minimal invasiveness and high spatiotemporal precision remains a formidable challenge. In this study, a multifunctional nano‐optical electrode (NOE) to mitigate depressive symptoms in animal models of depression is introduced. The NOEs' core–shell architecture integrates mesoporous carbon shells for optimal absorption of near‐infrared (NIR) light, alongside superparamagnetic ferric oxide nanocluster cores for magnetic resonance imaging (MRI) visibility. This configuration enables the precise excitation of untransfected neurons using NIR irradiation. The MRI‐guided NIR neuromodulation via NOEs can significantly alleviate depressive symptoms in mice. This is evidenced by the observed enhancement in pleasure‐seeking behaviors, improved motor functions, and a decrease in behaviors indicative of despair. The alleviation of depressive symptoms is ascribed to the NOEs' role as an efficient NIR light transducer, which boosts neuronal activity in the medial prefrontal cortex (mPFC). The MRI compatibility of the NOEs augments the spatial resolution, further refining the precision of neuromodulation. The multimodal, precise, transcranial, and non‐genetic approach of the NOEs‐based neuromodulation strategy heralds a new era in the optical‐theranostics of neurological disorders.

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Microglia-triggered hypoexcitability plasticity of pyramidal neurons in the rat medial prefrontal cortex

Cited by 12 publications

References 111 publications

Immune-Triggered Forms of Plasticity Across Brain Regions

Immune-Triggered Forms of Plasticity Across Brain Regions

Acute Cerebellar Inflammation and Related Ataxia: Mechanisms and Pathophysiology

Transcranial NIR Neuromodulation via Multifunctional Nano‐Optical Electrodes for Relieving Depressive Symptoms

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