Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, Royal Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands;
Department of Neuroscience Rita Levi-Montalcini, University of Turin, 10040 Turin, Italy.
Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6855-6865. doi: 10.1073/pnas.1916163117. Epub 2020 Mar 9.
Perineuronal nets (PNNs) are assemblies of extracellular matrix molecules, which surround the cell body and dendrites of many types of neuron and regulate neural plasticity. PNNs are prominently expressed around neurons of the deep cerebellar nuclei (DCN), but their role in adult cerebellar plasticity and behavior is far from clear. Here we show that PNNs in the mouse DCN are diminished during eyeblink conditioning (EBC), a form of associative motor learning that depends on DCN plasticity. When memories are fully acquired, PNNs are restored. Enzymatic digestion of PNNs in the DCN improves EBC learning, but intact PNNs are necessary for memory retention. At the structural level, PNN removal induces significant synaptic rearrangements in vivo, resulting in increased inhibition of DCN baseline activity in awake behaving mice. Together, these results demonstrate that PNNs are critical players in the regulation of cerebellar circuitry and function.
周围神经毡（PNNs）是细胞外基质分子的集合，它们包围着许多类型神经元的细胞体和树突，并调节神经可塑性。PNNs 在大脑深部核团（DCN）的神经元周围表达明显，但它们在成年小脑可塑性和行为中的作用还远不清楚。在这里，我们发现在眨眼条件反射（EBC）过程中，小鼠 DCN 中的 PNNs 减少，EBC 是一种依赖于 DCN 可塑性的联想运动学习形式。当记忆完全形成时，PNNs 会恢复。在 DCN 中消化 PNNs 可以改善 EBC 学习，但完整的 PNNs 对于记忆保留是必要的。在结构水平上，PNN 的去除会导致体内的突触重排，从而增加清醒活动小鼠中 DCN 基线活动的抑制。总的来说，这些结果表明 PNNs 是调节小脑回路和功能的关键因素。
