PT  - JOURNAL ARTICLE
AU  - Yulia Dembitskaya
AU  - Nikolay Gavrilov
AU  - Igor Kraev
AU  - Maxim Doronin
AU  - Olga Tyurikova
AU  - Alexey Semyanov
TI  - Attenuation of the extracellular matrix increases the number of synapses but suppresses synaptic plasticity
AID  - 10.1101/2020.04.23.058115
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.23.058115
4099  - http://biorxiv.org/content/early/2020/05/03/2020.04.23.058115.short
4100  - http://biorxiv.org/content/early/2020/05/03/2020.04.23.058115.full
AB  - The brain extracellular matrix (ECM) is a proteoglycan complex that occupies the extracellular space between brain cells and regulates brain development, brain wiring, and synaptic plasticity. However, the action of the ECM on synaptic plasticity remains controversial. Here, we employed serial section electron microscopy to show that enzymatic attenuation of ECM with chondroitinase ABC (ChABC) triggers the appearance of new glutamatergic synapses onto thin dendritic spines of CA1 pyramidal neurons. The appearance of new synapses increased the ratio of the field excitatory postsynaptic potential (fEPSP) to presynaptic fiber volley (PrV), suggesting that these new synapses are formed on existing axonal fibers. However, both the mean miniature excitatory postsynaptic current (mEPSC) amplitude and AMPA/NMDA ratio were decreased, suggesting that ECM attenuation increased the proportion of ‘unpotentiated’ synapses. A higher proportion of unpotentiated synapses would be expected to promote long-term potentiation (LTP). Surprisingly, theta-burst induced LTP was suppressed by ChABC treatment. The suppression of LTP was accompanied by decreased excitability of CA1 pyramidal neurons due to the upregulation of small conductance Ca2+-activated K+ (SK) channels. A pharmacological blockade of SK channels restored cell excitability and, expectedly, enhanced LTP above the level of control. This enhancement of LTP was abolished by a blockade of Rho-associated protein kinase (ROCK), which is involved in the maturation of dendritic spines. Thus, ECM attenuation enables the appearance of new synapses in the hippocampus, which is compensated for by a reduction in the excitability of postsynaptic neurons, thereby preventing network overexcitation at the expense of synaptic plasticity.Competing Interest StatementThe authors have declared no competing interest.