The voltage-gated Ca2+ channel subunit α2δ-4 regulates locomotor behavior and sensorimotor gating in mice.
The voltage-gated Ca2+ channel subunit α2δ-4 regulates locomotor behavior and sensorimotor gating in mice.
复制标题
DOI：
10.1371/journal.pone.0263197
复制
发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
Lee A
中科院分区：
文献类型：
--
作者：
Klomp A;Omichi R;Iwasa Y;Smith RJ;Usachev YM;Russo AF;Narayanan NS;Lee A
电压门控性Ca 2+通道对于神经系统的发育和成熟功能至关重要。编码这些通道的α2δ-4辅助亚基的CACNA 2D 4基因的变体与神经精神和神经发育障碍相关。α2δ-4在视网膜中显著表达，对视力至关重要，但尚未研究α2δ-4的视网膜外功能。在这里，我们试图通过分析α2δ-4敲除（KO）小鼠的行为表型来填补这一空白。α2δ-4 KO小鼠（雄性和雌性）在前脉冲抑制中表现出显著损伤，这不太可能由听觉脑干反应阈值适度升高引起。尽管两种性别的α2δ-4 KO小鼠在各种试验中表现出过度活跃，但在转棒试验中仅雌性显示出运动协调受损。α2δ-4 KO小鼠在高架十字迷宫和悬尾试验中分别表现出抗焦虑和抗抑郁行为。我们的研究结果揭示了α2δ-4在感觉运动门控和运动功能中的意想不到的作用，并将α2δ-4 KO小鼠鉴定为研究与CACNA 2D 4变体相关的病理生理学的新模型。
Voltage-gated Ca2+ channels are critical for the development and mature function of the nervous system. Variants in the CACNA2D4 gene encoding the α2δ-4 auxiliary subunit of these channels are associated with neuropsychiatric and neurodevelopmental disorders. α2δ-4 is prominently expressed in the retina and is crucial for vision, but extra-retinal functions of α2δ-4 have not been investigated. Here, we sought to fill this gap by analyzing the behavioral phenotypes of α2δ-4 knockout (KO) mice. α2δ-4 KO mice (both males and females) exhibited significant impairments in prepulse inhibition that were unlikely to result from the modestly elevated auditory brainstem response thresholds. Whereas α2δ-4 KO mice of both sexes were hyperactive in various assays, only females showed impaired motor coordination in the rotarod assay. α2δ-4 KO mice exhibited anxiolytic and anti-depressive behaviors in the elevated plus maze and tail suspension tests, respectively. Our results reveal an unexpected role for α2δ-4 in sensorimotor gating and motor function and identify α2δ-4 KO mice as a novel model for studying the pathophysiology associated with CACNA2D4 variants.
登录
查看更多内容
DOI：
10.1113/jp272262
发表时间：
2016-10-01
期刊：
The Journal of physiology
影响因子：
--
作者：
Dolphin AC
通讯作者：
Dolphin AC
影响因子：
5.3
作者：
Kerov, Vasily;Laird, Joseph G.;Lee, Amy
通讯作者：
Lee, Amy
影响因子：
4.8
作者：
Lee, Amy;Wang, Shiyi;Haeseleer, Francoise
通讯作者：
Haeseleer, Francoise
影响因子：
3.3
作者：
Ellenbroek, BA;Budde, S;Cools, AR
通讯作者：
Cools, AR
影响因子：
3.9
作者：
MANJIVIONA, J;PRIOR, M
通讯作者：
PRIOR, M