Department of Molecular Neurobiology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street 16/10, Moscow, 117997, Russia.
Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, 603950, Russia.
Cell Calcium. 2021 Jun;96:102406. doi: 10.1016/j.ceca.2021.102406. Epub 2021 Apr 8.
The effect of brain extracellular matrix (ECM) on synaptic plasticity remains controversial. Here, we show that targeted enzymatic attenuation with chondroitinase ABC (ChABC) of ECM triggers the appearance of new glutamatergic synapses on hippocampal pyramidal neurons, thereby increasing the amplitude of field EPSPs while decreasing both the mean miniature EPSC amplitude and AMPA/NMDA ratio. Although the increased proportion of 'unpotentiated' synapses caused by ECM attenuation should promote long-term potentiation (LTP), surprisingly, LTP was suppressed. The upregulation of small conductance Ca-activated K (SK) channels decreased the excitability of pyramidal neurons, thereby suppressing LTP. A blockade of SK channels restored cell excitability and enhanced LTP; this enhancement was abolished by a blockade of Rho-associated protein kinase (ROCK), which is involved in the maturation of dendritic spines. Thus, targeting ECM elicits the appearance of new synapses, which can have potential applications in regenerative medicine. However, this process is compensated for by a reduction in postsynaptic neuron excitability, preventing network overexcitation at the expense of synaptic plasticity.
脑细胞外基质（ECM）对突触可塑性的影响仍存在争议。在这里，我们发现靶向酶解 ECM 中的软骨素酶 ABC（ChABC）会触发海马锥体神经元上新的谷氨酸能突触的出现，从而增加场兴奋性突触后电位（EPSP）的幅度，同时降低平均微小 EPSC 幅度和 AMPA/NMDA 比值。尽管 ECM 减弱引起的“未增强”突触比例的增加应该会促进长时程增强（LTP），但令人惊讶的是，LTP 受到了抑制。小电导钙激活钾（SK）通道的上调降低了锥体神经元的兴奋性，从而抑制了 LTP。阻断 SK 通道恢复了细胞兴奋性并增强了 LTP；阻断 Rho 相关蛋白激酶（ROCK）消除了这种增强作用，ROCK 参与树突棘的成熟。因此，靶向 ECM 会引发新突触的出现，这在再生医学中有潜在的应用。然而，这种过程会通过减少突触后神经元的兴奋性来进行补偿，从而以牺牲突触可塑性为代价防止网络过度兴奋。
