Reduced GABAergic inhibition and impaired synapse elimination by neuroligin-2 deletion from Purkinje cells of the developing cerebellum.

IF 3.4 3区 医学 Q2 NEUROSCIENCES
Frontiers in Neural Circuits Pub Date : 2025-03-14 eCollection Date: 2025-01-01 DOI:10.3389/fncir.2025.1530141
Esther Suk King Lai, Naofumi Uesaka, Taisuke Miyazaki, Kouichi Hashimoto, Masahiko Watanabe, Masanobu Kano
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引用次数: 0

Abstract

Functionally mature neural circuits are shaped during postnatal development by eliminating redundant synapses formed around birth. This process is known as synapse elimination and requires a proper balance of excitation and inhibition. Neuroligin-2 (NL2) is a postsynaptic cell adhesion molecule required for the formation, maintenance, and function of inhibitory synapses. However, how NL2 regulates synapse elimination during postnatal development is largely unknown. Here we report that the deletion of NL2 from Purkinje cells (PCs) in the cerebellum impairs the developmental elimination of redundant climbing fiber (CF) to PC synapses. In global NL2-knockout (KO) mice, GABAergic inhibition to PCs was attenuated and CF synapse elimination was impaired after postnatal day 10 (P10). These phenotypes were restored by the expression of NL2 into PCs of NL2-KO mice. Moreover, microRNA-mediated knockdown of NL2 specifically from PCs during development caused attenuated inhibition and impaired CF synapse elimination. In PCs innervated by "strong" and "weak" CFs, calcium transients elicited by "weak" CFs were enhanced in NL2-deficient PCs, suggesting that excess calcium signaling permits the survival of redundant "weak" CF synapses. We conclude that NL2 is crucial for maintaining inhibitory synaptic function and properly eliminating redundant CF synapses during postnatal development.

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来源期刊
CiteScore
6.00
自引率
5.70%
发文量
135
审稿时长
4-8 weeks
期刊介绍: Frontiers in Neural Circuits publishes rigorously peer-reviewed research on the emergent properties of neural circuits - the elementary modules of the brain. Specialty Chief Editors Takao K. Hensch and Edward Ruthazer at Harvard University and McGill University respectively, are supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics and the public worldwide. Frontiers in Neural Circuits launched in 2011 with great success and remains a "central watering hole" for research in neural circuits, serving the community worldwide to share data, ideas and inspiration. Articles revealing the anatomy, physiology, development or function of any neural circuitry in any species (from sponges to humans) are welcome. Our common thread seeks the computational strategies used by different circuits to link their structure with function (perceptual, motor, or internal), the general rules by which they operate, and how their particular designs lead to the emergence of complex properties and behaviors. Submissions focused on synaptic, cellular and connectivity principles in neural microcircuits using multidisciplinary approaches, especially newer molecular, developmental and genetic tools, are encouraged. Studies with an evolutionary perspective to better understand how circuit design and capabilities evolved to produce progressively more complex properties and behaviors are especially welcome. The journal is further interested in research revealing how plasticity shapes the structural and functional architecture of neural circuits.
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