Synaptic receptors and plasticity

我们通过产生缺乏谷氨酸受体(GluRs)的突变小鼠来研究突触可塑性与神经发育、学习和记忆的关系。Glurε1亚单位突变小鼠在Morris水迷宫中表现出海马长时程增强和空间学习障碍。Glurε2亚单位突变阻碍了脑干三叉神经核中与胡须相关的神经元桶状结构的形成和海马区突触的可塑性。Glurδ2亚基选择性地定位于小脑浦肯野细胞，对小脑LTD、运动协调、运动学习、平行纤维-浦肯野细胞突触的稳定性以及多个攀爬纤维(CF)的消除在发育过程中是必不可少的。代谢型GluR1突变小鼠在小脑LTD、联合瞬目条件反射和CF消除方面存在缺陷。多发性CFs的PKCγ突变小鼠眨眼条件反射正常。这些结果表明，突触的可塑性是某种形式学习和记忆的细胞基础。他们还表明，GluRs在大脑发育过程中的神经网络形成和高级大脑功能中发挥着重要作用，这意味着这些过程具有共同的分子机制。

We investigated the relationship of synaptic plasticity to neural development, learning and memory by generating mutant mice lacking glutamate receptors (GluRs). The GluRε1 subunit mutant mice showed the decreased hippocampal LTP and impaired spatial learning in the Morris water maze. The GluRε2 subunit mutation hindered the formation of the whisker-related neuronal barrelette structure in the brainstem trigeminal nucleus and synaptic plasticity in the hippocampus. The GluRδ2 subunit selectively localized in cerebellar Purkinje cells was essential for cerebellarLTD, motor coordination, motor learning, stability of parallel fiber-Purkinje cell synapses and elimination of multiple climbing fibers (CF) during development. Metabotropic GluR1 mutant mice were defective in cerebellar LTD, associative eyeblink conditioning and CF elimination. Eyeblink conditioning was normal in PKCγ mutant mice with multiple CFs. These results suggest that synaptic plasticity is the cellular basis of a certain form of learning and memory. They also suggest that GluRs play important roles in neural network formation during brain development and in higher brain function, implying that these processes share common molecular mechanisms.