Deletion of glycine transporter 1 (GlyT1) in forebrain neurons facilitates reversal learning: enhanced cognitive adaptability?
Deletion of glycine transporter 1 (GlyT1) in forebrain neurons facilitates reversal learning: enhanced cognitive adaptability?
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DOI：
10.1037/a0016676
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发表时间：
2009-10
影响因子：
1.9
通讯作者：
Yee, Benjamin K.
中科院分区：
文献类型：
--
作者：
Singer, Philipp;Boison, Detlev;Moehler, Hanns;Feldon, Joram;Yee, Benjamin K.
N-甲基-d-天冬氨酸受体（NMDAR）附近甘氨酸的局部可用性部分受神经元甘氨酸转运蛋白1（GlyT 1）调节，因此可以调节NMDAR功能，因为与NMDAR的甘氨酸位点结合是通道激活所必需的。破坏前脑神经元中的GlyT 1已被证明可以增强巴甫洛夫条件反射和物体识别记忆。在这里，我们报告说，同样的遗传操作促进了参考记忆的水迷宫测试中的逆转学习，但没有导致任何明显的改善工作记忆版本的水迷宫测试。还观察到在T-迷宫上进行的非空间辨别反转任务中的促进作用，支持前脑神经元GlyT 1可能调节（新）学习和相关记忆功能的灵活性的结论。一种可能性是，这些表型可能反映了对某些形式的前摄干扰的易感性降低。这可能与GlyT 1抑制剂在治疗认知缺陷（包括精神分裂症）中的建议临床应用相关，精神分裂症的特征是除了疾病的阳性症状外还具有认知障碍。
Local availability of glycine near N-methyl-d-aspartate receptors (NMDARs) is partly regulated by neuronal glycine transporter 1 (GlyT1), which can therefore modulate NMDAR function because binding to the glycine site of the NMDAR is necessary for channel activation. Disrupting GlyT1 in forebrain neurons has been shown to enhance Pavlovian conditioning and object recognition memory. Here, we reported that the same genetic manipulation facilitated reversal learning in the water maze test of reference memory, but did not lead to any clear improvement in a working memory version of the water maze test. Facilitation in a non-spatial discrimination reversal task conducted on a T-maze was also observed, supporting the conclusion that forebrain neuronal GlyT1 may modulate the flexibility in (new) learning and relevant mnemonic functions. One possibility is that these phenotypes may reflect reduced susceptibility to certain forms of proactive interference. This may be relevant for the suggested clinical application of GlyT1 inhibitors in the treatment of cognitive deficits, including schizophrenia, which is characterized by cognitive inflexibility in addition to the positive symptoms of the disease.
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