☆ 4.7 Review

Focusing on the Emerging Role of Kainate Receptors in the Dorsal Cochlear Nucleus (DCN) and Cerebellum

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

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Summary: Kainate receptors (KARs) play a crucial role in regulating synaptic circuits through ionotropic or metabotropic mechanisms. This study reveals that the acute convulsive effect of kainate is primarily dependent on GluK2/GluK5 containing KARs, while the convulsive activity induced by pilocarpine and pentylenetetrazol is not affected by the absence of KARs. Interestingly, the genetic inactivation of GluK2 increases susceptibility to acute pilocarpine-induced seizures.

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Summary: This study provides the first direct evidence of functional extrasynaptic kainate receptors (KARs) on mossy cells (MCs) in the hippocampus. These KARs are mainly located extrasynaptically and play a critical role in the activity of MCs. Increases in ambient glutamate can activate the KARs on MCs.

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CRISPR-Cas13-Mediated Knockdown of Regulator of G-Protein Signaling 8 (RGS8) Does Not Affect Purkinje Cell Dendritic Development

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Summary: In this study, CRISPR-Cas13 technology was used to study gene function in differentiating neurons by targeting RGS8. The results showed that CRISPR-Cas13-mediated knockdown did not significantly affect the dendritic growth of Purkinje cells, establishing it as a reliable method for studying gene function in primary neurons.

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The Emerging Key Role of the mGluR1-PKCγ Signaling Pathway in the Pathogenesis of Spinocerebellar Ataxias: A Neurodevelopmental Viewpoint

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Summary: Synaptic plasticity, characterized as key processes allowing the brain to operate dynamically, involves various modulators including kainate receptors, which play an important role in regulating neurotransmitter release and bidirectionally modulating plasticity.

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Summary: Kainate receptors (KARs) mediate both ionotropic currents and metabotropic signalling. They regulate GABA release in the hippocampus bidirectionally through ionotropic and metabotropic pathways, affecting the strength of inhibition. This evidence suggests that KARs play a crucial role in regulating the balance between excitation and inhibition in neural circuits.

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Modulation of Increased mGluR1 Signaling by RGS8 Protects Purkinje Cells From Dendritic Reduction and Could Be a Common Mechanism in Diverse Forms of Spinocerebellar Ataxia

Qin-Wei Wu et al.

Summary: RGS8 has been identified as a key mediator in the pathogenesis of SCAs, affecting the mGluR1 pathway in Purkinje cells. Overexpression of RGS8 can partially counteract the negative effects of DHPG-induced dendrite expansion in Purkinje cells.

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The Lbx1 lineage differentially contributes to inhibitory cell types of the dorsal cochlear nucleus, a cerebellum-like structure, and the cerebellum

Friedrich Schinzel et al.

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The Bacterial Enzyme Cas13 Interferes with Neurite Outgrowth from Cultured Cortical Neurons

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Nandish Khanra et al.

Summary: The study presents the first structure of a KAR heteromer, showing how GluK2 subunits undergo structural rearrangements during desensitization to facilitate channel closure. It also reveals that the large conformational differences between antagonist-bound and desensitized states are mediated by the linkers connecting the pore helices to the ligand binding domains.

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Clustered mutations in the GRIK2 kainate receptor subunit gene underlie diverse neurodevelopmental disorders

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Summary: Variants in the GRIK2 gene can lead to a neurodevelopmental disorder characterized by intellectual disability and developmental delay, with different outcomes depending on mono-allelic or bi-allelic effects. Shared GRIK2 variants among patients are associated with overlapping behavioral and neurological dysfunctions, indicating the pathogenic nature of these mutations. Functional studies on mutant GRIK2 variants in Kainate receptors reveal complex effects on receptor properties and contribute to a better understanding of the role of KARs in early nervous system development.

AMERICAN JOURNAL OF HUMAN GENETICS (2021)

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Conditional gene silencing via a CRISPR system in cerebellar Purkinje cells

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Serine/threonine kinase 17b (STK17B) signalling regulates Purkinje cell dendritic development and is altered in multiple spinocerebellar ataxias

Qin-Wei Wu et al.

Summary: STK17B is strongly expressed in cerebellar Purkinje cells and is regulated by PKC phosphorylation. It acts as a downstream effector of PKC, influencing the morphological changes of Purkinje cells and possibly playing a role in the pathology of SCAs.

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Kainate receptors regulate the functional properties of young adult-born dentate granule cells

Yiwen Zhu et al.

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Cerebellar Development and Circuit Maturation: A Common Framework for Spinocerebellar Ataxias

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Kainate Receptors Coexist in a Functional Complex with KCC2 and Regulate Chloride Homeostasis in Hippocampal Neurons

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Kainate receptor-mediated depression of glutamatergic transmission involving protein kinase A in the lateral amygdala

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Inhibitory and excitatory subtypes of cochlear nucleus neurons are defined by distinct bHLH transcription factors, Ptf1a and Atoh1

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Functional maturation of CA1 synapses involves activity-dependent loss of tonic kainate receptor-mediated inhibition of glutamate release

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Glutamate receptor agonist kainate enhances primary dendrite number and length from immature mouse cortical neurons in vitro

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Purkinje-like cells in the cochlear nucleus of the Common Tree Shrew (Tupaia glis) identified by calbindin immunohistochemistry

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Kainate receptors differentially regulate release at two parallel fiber synapses

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Subunit composition of kainate receptors in hippocampal interneurons

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Synaptic activation of presynaptic kainate receptors on hippocampal mossy fiber synapses

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Kainate receptor-mediated synaptic currents in cerebellar Golgi cells are not shaped by diffusion of glutamate

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GluR5 and GluR6 kainate receptor subunits coexist in hippocampal neurons and coassemble to form functional receptors

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