Attenuation of the extracellular matrix increases the number of synapses but suppresses synaptic plasticity through upregulation of SK channels. (June 2021)

• Record Type: Journal Article
• Authors: Dembitskaya, Yulia; Gavrilov, Nikolay; Kraev, Igor; Doronin, Maxim; Tang, Yong; Li, Li; Semyanov, Alexey
• Is Part Of: Cell calcium. Volume 96(2021)
• Publication Date: 2021-06
• Subjects: Extracellular matrix -- Dendritic spine -- SK channel -- LTP; Calcium -- Metabolism -- Periodicals; Vertebrates -- Physiology -- Periodicals; Calcium -- Physiological effect -- Periodicals; Cell physiology -- Periodicals; Calcium in the body -- Periodicals; 572.516
• DOI: 10.1016/j.ceca.2021.102406
• Languages: English
• ISSNs: 0143-4160

Abstract

Graphical abstract: Highlights: ECM attenuation triggers the appearance of new synapses in the hippocampus. GABAergic signalling remains unaffected. Excitability of pyramidal neurons and LTP are reduced by SK channels. Blockade of SK channels reveals enhanced LTP. LTP enhancement is mediated by the ROCK pathway. Abstract: 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 2+ -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.