Área de Psicobiología, Universitat Jaume I, Facultat de Ciencies de la Salut, Avenida Vicente Sos Baynat sn, 12071, Castellón de la Plana, Spain.
Área de Psicobiología, Universitat Jaume I, Facultat de Ciencies de la Salut, Avenida Vicente Sos Baynat sn, 12071, Castellón de la Plana, Spain.
Neuropharmacology. 2022 Nov 1;218:109210. doi: 10.1016/j.neuropharm.2022.109210. Epub 2022 Aug 17.
Perineuronal nets (PNNs) are cartilage-like structures of extracellular matrix molecules that enwrap in a net-like manner the cell-body and proximal dendrites of special subsets of neurons. PNNs stabilize their incoming connections and restrict plasticity. Consequently, they have been proposed as a candidate mechanism for drug-induced learning and memory. In the cerebellum, PNNs surround Golgi inhibitory interneurons and both inhibitory and excitatory neurons in the deep cerebellar nuclei (DCN). Previous studies from the lab showed that cocaine-induced conditioned memory increased PNN expression in the granule cell layer of the posterior vermis. The present research aimed to investigate the role of cerebellar PNNs in cocaine-induced conditioned preference. For this purpose, we use the enzyme chondroitinase ABC (ChABC) to digest PNNs at different time points of the learning process to ascertain whether their removal can affect drug-induced memory. Our results show that PNN digestion using ChABC in the posterior vermis (Lobule VIII) did not affect the acquisition of cocaine-induced conditioned preference. However, the removal of PNNs in Lobule VIII -but not in the DCN- disrupted short-term memory of conditioned preference. Moreover, although PNN digestion facilitated the formation of extinction, reinstatement of cocaine-induced conditioned preference was encouraged under PNN digestion. The present findings suggests that PNNs around Golgi interneurons are needed to maintain cocaine-induced Pavlovian memory but also to stabilize extinction memory. Conversely, PNN degradation within the DCN did not affect stability of cocaine-induced memories. Therefore, degradation of PNNs in the vermis might be used as a promising tool to manipulate drug-induced memory.
周围神经毡 (PNNs) 是细胞外基质分子的软骨样结构，以网状方式包裹特殊神经元亚群的细胞体和近端树突。PNNs 稳定传入的连接并限制可塑性。因此，它们被提出作为药物诱导学习和记忆的候选机制。在小脑，PNNs 围绕着高尔基抑制性中间神经元和深小脑核 (DCN) 中的抑制性和兴奋性神经元。实验室的先前研究表明，可卡因诱导的条件记忆增加了后叶颗粒层的 PNN 表达。本研究旨在探讨小脑 PNN 在可卡因诱导的条件偏好中的作用。为此，我们使用酶软骨素酶 ABC (ChABC) 在学习过程的不同时间点消化 PNNs，以确定它们的去除是否会影响药物诱导的记忆。我们的结果表明，ChABC 在小脑后叶（VIII 叶）中消化 PNNs 不会影响可卡因诱导的条件偏好的获得。然而，在 VIII 叶而不是 DCN 中去除 PNNs 破坏了条件偏好的短期记忆。此外，尽管 PNN 消化促进了消退的形成，但在 PNN 消化下，可卡因诱导的条件偏好的复现得到了鼓励。这些发现表明，高尔基中间神经元周围的 PNNs 不仅需要维持可卡因诱导的巴甫洛夫记忆，而且需要稳定消退记忆。相反，DCN 内 PNN 的降解不影响可卡因诱导记忆的稳定性。因此，小脑蚓部 PNNs 的降解可能被用作操纵药物诱导记忆的有前途的工具。
