A novel role for the ADHD risk gene latrophilin-3 in learning and memory in Lphn3 knockout rats

被引：18

作者：

Regan, Samantha L. ^{[1
,2
]}

Pitzer, Emily M. ^{[1
,2
]}

Hufgard, Jillian R. ^{[1
,2
]}

Sugimoto, Chiho ^{[1
,2
]}

Williams, Michael T. ^{[1
,2
]}

Vorhees, Charles V. ^{[1
,2
]}

机构：

[1] Univ Cincinnati, Dept Pediat, Coll Med, Cincinnati, OH 45229 USA

[2] Cincinnati Childrens Res Fdn, Div Neurol, MLC 7044,3333 Burnet Ave, Cincinnati, OH 45229 USA

来源：

NEUROBIOLOGY OF DISEASE | 2021年 / 158卷

关键词：

Lphn3; Adgrl-3; Lphn3 knockout rat; Cognition; Long-term potentiation; Spatial learning and memory; Egocentric learning; Novel object recognition; CINCINNATI WATER MAZE; DEFICIT HYPERACTIVITY DISORDER; MEDIAL PREFRONTAL CORTEX; ALPHA-LATROTOXIN; ATTENTION-DEFICIT; RECOGNITION MEMORY; MICE NULL; RECEPTOR; LPHN3; LATROPHILIN;

D O I：

10.1016/j.nbd.2021.105456

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页数：11

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