A novel role for the ADHD risk gene latrophilin-3 in learning and memory in Lphn3 knockout rats.
A novel role for the ADHD risk gene latrophilin-3 in learning and memory in Lphn3 knockout rats.
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DOI：
10.1016/j.nbd.2021.105456
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发表时间：
2021-10
影响因子：
6.1
通讯作者：
Vorhees CV
中科院分区：
文献类型：
--
作者：
Regan SL;Pitzer EM;Hufgard JR;Sugimoto C;Williams MT;Vorhees CV
嗜Latrophilins （lphn）是具有三种亚型的粘附G蛋白偶联受体，但只有LPHN3是脑特异性的（尾状核、前额叶皮层、齿状核、杏仁核和小脑）。LPHN3的变异与ADHD有关。Lphn3在大鼠、小鼠、斑马鱼和果蝇中的零突变导致多动症，但其在学习和记忆（L&M）中的作用在很大程度上是未知的。利用Lphn3敲除（KO）大鼠，我们检测了来自杂合育种对的认知能力、CA1的长期增强（LTP）、NMDA受体表达和神经组织学。KO大鼠在辛辛那提水迷宫中的自我中心L&M、Morris水迷宫中的空间L&M和认知灵活性受到损害，但对条件冻结、新物体识别或时间顺序识别没有影响。ko相关的运动过度活动对游泳速度没有影响。KO大鼠早期ltp减少，但晚期ltp没有减少，海马NMDA-NR1表达减少。在第二个实验中，KO大鼠对光预脉冲的反应先于声惊吓脉冲，反映了视觉信号的检测。在第三个实验中，给予额外的MWM预训练和隐藏平台过度训练的KO大鼠没有达到WT大鼠的学习水平。Nissl组织学显示KO大鼠无结构异常。LPHN3对自我中心和异位中心记忆有选择性影响，但对条件冻结和识别记忆没有影响。
Latrophilins (LPHNs) are adhesion G protein-coupled receptors with three isoforms but only LPHN3 is brain specific (caudate, prefrontal cortex, dentate, amygdala, and cerebellum). Variants of LPHN3 are associated with ADHD. Null mutations of Lphn3 in rat, mouse, zebrafish, and Drosophila result in hyperactivity, but its role in learning and memory (L&M) is largely unknown. Using our Lphn3 knockout (KO) rats we examined the cognitive abilities, long-term potentiation (LTP) in CA1, NMDA receptor expression, and neurohistology from heterozygous breeding pairs. KO rats were impaired in egocentric L&M in the Cincinnati water maze, spatial L&M and cognitive flexibility in the Morris water maze (MWM), with no effects on conditioned freezing, novel object recognition, or temporal order recognition. KO-associated locomotor hyperactivity had no effect on swim speed. KO rats had reduced early-LTP but not late-LTP and had reduced hippocampal NMDA-NR1 expression. In a second experiment, KO rats responded to a light prepulse prior to an acoustic startle pulse, reflecting visual signal detection. In a third experiment, KO rats given extra MWM pretraining and hidden platform overtraining showed no evidence of reaching WT rats’ levels of learning. Nissl histology revealed no structural abnormalities in KO rats. LPHN3 has a selective effect on egocentric and allocentric L&M without effects on conditioned freezing or recognition memory.
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影响因子：
11
作者：
Franke, B.;Faraone, S. V.;Asherson, P.;Buitelaar, J.;Bau, C. H. D.;Ramos-Quiroga, J. A.;Mick, E.;Grevet, E. H.;Johansson, S.;Haavik, J.;Lesch, K-P;Cormand, B.;Reif, A.
通讯作者：
Reif, A.
影响因子：
3.7
作者：
Braun, Amanda A.;Amos-Kroohs, Robyn M.;Williams, Michael T.
通讯作者：
Williams, Michael T.
DOI：
10.1002/ajmg.b.31141
发表时间：
2011-01-01
影响因子：
2.8
作者：
Domene, Sabina;Stanescu, Horia;Muenke, Maximilian
通讯作者：
Muenke, Maximilian
影响因子：
3.5
作者：
Hwang, In Wook;Lim, Myung Ho;Jin, Han Jun
通讯作者：
Jin, Han Jun
影响因子：
2
作者：
Acosta MT;Swanson J;Stehli A;Molina BS;MTA Team;Martinez AF;Arcos-Burgos M;Muenke M
通讯作者：
Muenke M