Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha NE 68198.
Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE 68198
eNeuro. 2023 Mar 27;10(3). doi: 10.1523/ENEURO.0364-22.2023. Print 2023 Mar.
Motor skill learning induces changes in synaptic structure and function in the primary motor cortex (M1). In the fragile X syndrome (FXS) mouse model an impairment in motor skill learning and associated formation of new dendritic spines was previously reported. However, whether modulation of synaptic strength through trafficking of AMPA receptors (AMPARs) with motor skill training is impaired in FXS is not known. Here, we performed imaging of a tagged AMPA receptor subunit, GluA2, in layer (L)2/3 neurons in the primary motor cortex of wild-type (WT) and knock-out (KO) male mice at different stages of learning a single forelimb-reaching task. Surprisingly, in the KO mice, despite impairments in learning there was no deficit in motor skill training-induced spine formation. However, the gradual accumulation of GluA2 in WT stable spines, which persists after training is completed and past the phase of spine number normalization, is absent in the KO mouse. These results demonstrate that motor skill learning not only reorganizes circuits through formation of new synapses, but also strengthens existing synapses through accumulation of AMPA receptors and GluA2 changes are better associated with learning than new spine formation.
运动技能学习会引起初级运动皮层（M1）中突触结构和功能的变化。在脆性 X 综合征（FXS）小鼠模型中，先前报道了运动技能学习受损和相关新树突棘形成。然而，运动技能训练是否会通过 AMPA 受体（AMPAR）的运输来调节突触强度在 FXS 中受损尚不清楚。在这里，我们在野生型（WT）和敲除（KO）雄性小鼠的初级运动皮层 L2/3 神经元中，对标记的 AMPA 受体亚基 GluA2 进行了成像，以观察它们在学习单次前肢伸展任务的不同阶段的情况。令人惊讶的是，在 KO 小鼠中，尽管学习能力受损，但运动技能训练诱导的棘突形成并没有缺陷。然而，在 WT 稳定棘突中，GluA2 的逐渐积累在训练完成后并且在棘突数量正常化阶段之后仍然存在，但在 KO 小鼠中却不存在。这些结果表明，运动技能学习不仅通过形成新的突触来重组回路，而且还通过 AMPA 受体的积累来增强现有的突触，并且 GluA2 的变化与学习的相关性比新棘突的形成更好。
