Improvements in hippocampal-dependent learning and decremental attention in 5-HT3 receptor overexpressing mice
Improvements in hippocampal-dependent learning and decremental attention in 5-HT3 receptor overexpressing mice
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DOI：
10.1101/lm.56103
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发表时间：
2003-09-01
影响因子：
2
通讯作者：
Allan, AM
中科院分区：
文献类型：
--
作者：
Harrell, AV;Allan, AM
5-羟色胺的S-HT 3受体在边缘结构内表达，并且已知调节神经递质释放，表明该受体可能影响学习和记忆。多巴胺能神经传递的紊乱会导致注意力、学习和记忆能力的改变。为了研究S-HT 3受体在学习、记忆和注意力中的作用，在巴甫洛夫情境和线索恐惧条件反射、恐惧消退和潜伏抑制（LI）范式中测试了5-HT 3受体过表达（5-HT 3-OE）转基因小鼠及其野生型同窝小鼠（WT）。评估前脉冲抑制（PPI）以揭示感觉运动门控的变化。此外，还评估了焦虑行为、休克敏感性和对新刺激的反应。5-HT 3-OE小鼠表现出增强的情境条件反射，而线索条件反射保持与WT小鼠相同。5-HT 3-OE小鼠在环境或线索的消退率方面与WT没有差异。与WT相比，5-HT 3-OE小鼠的LI增强。PPI保持不变。然而，5-HT 3-OE小鼠在高架十字迷宫中表现出对新环境刺激的探索行为增强和焦虑减少。结果表明，小鼠前脑中S-HT 3受体的过表达导致增强的大脑皮层依赖性学习和注意力。对新奇事物的反应增强的检查行为可能有助于由于5-HT 3受体过表达而观察到的学习，记忆和注意力的改善。
The S-HT3 receptor for serotonin is expressed within limbic structures and is known to modulate neurotransmitter release, suggesting that this receptor may influence learning and memory. Perturbations in serotonergic neurotransmission lead to changes in the ability to attend, learn, and remember. To examine the role of S-HT3 receptors in learning, memory, and attention, 5-HT3 receptor overexpressing (5-HT3-OE) transgenic mice and their wild-type littermates (WT) were tested in Pavlovian contextual and cued fear conditioning, fear extinction, and latent inhibition (LI) paradigms. Prepulse inhibition (PPI) was assessed to reveal changes in sensorimotor gating. Additionally, anxious behaviors, shock sensitivity, and reactions to novel stimuli were evaluated. 5-HT3-OE mice displayed enhanced contextual conditioning, whereas cued conditioning remained the same as that of WT mice. 5-HT3-OE mice did not differ from WT in extinction rates to either the context or cue. LI was enhanced for 5-HT3-OE mice compared to WT. PPI remained unchanged. No differences in sensitivity to footshock or startle were found. However, 5-HT3-OE mice demonstrated heightened exploratory behavior in response to novel environmental stimuli and decreased anxiety as measured in the elevated plus-maze. Results indicate that overexpression of the S-HT3 receptor in mouse forebrain results in enhanced hippocampal-dependent learning and attention. Enhanced inspective behavior in response to novelty may contribute to the observed improvements in learning, memory, and attention due to 5-HT3 receptor overexpression.