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 Ca²⁺-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有争议。在这里，我们展示了 ECM 的软骨素酶 ABC (ChABC) 的靶向酶促衰减触发了海马锥体神经元上新谷氨酸能突触的出现，从而增加了场 EPSP 的幅度，同时降低了平均微型 EPSC 幅度和 AMPA/NMDA 比率。尽管由 ECM 衰减引起的“未增强”突触的比例增加应该促进长时程增强 (LTP)，但令人惊讶的是，LTP 被抑制了。小电导 Ca ²⁺激活的 K ⁺的上调(SK) 通道降低锥体神经元的兴奋性，从而抑制 LTP。SK 通道的阻断恢复了细胞的兴奋性并增强了 LTP；这种增强被 Rho 相关蛋白激酶 (ROCK) 的阻断所消除，ROCK 参与树突棘的成熟。因此，靶向 ECM 会引发新突触的出现，这在再生医学中具有潜在的应用价值。然而，这一过程通过突触后神经元兴奋性的降低得到补偿，以牺牲突触可塑性为代价防止网络过度兴奋。