Biology subjects

Kraev, I.

Publications and source records attributed to Kraev, I..

3 recordsLinked to original sources

bioRxiv2020

Attenuation of the extracellular matrix increases the number of synapses but suppresses synaptic plasticity

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.

neuroscience↗

bioRxiv2018

Astroglia withdraw from potentiated synapses boosting inter-synaptic cross-talk

Extrasynaptic actions of glutamate are limited by high-affinity transporters on perisynaptic astroglial processes (PAPs), which helps to maintain point-to-point transmission in excitatory circuits. Memory formation in the brain is associated with synaptic remodelling, but how this remodelling affects PAPs and therefore extrasynaptic glutamate actions is poorly understood. Here we used advanced imaging methods, in situ and in vivo, to find that a classical synaptic memory mechanism, long-term potentiation (LTP), triggers withdrawal of PAPs from potentiated synapses. Optical glutamate sensors combined with patch-clamp and 3D molecular localisation reveal that LTP induction thus prompts a spatial retreat of glial glutamate transporters, boosting glutamate spillover and NMDA receptor-mediated inter-synaptic cross-talk. The LTP-triggered PAP withdrawal involves NKCC1 transporters and the actin-controlling protein cofilin but does not depend on major Ca2+-dependent cascades in astrocytes. We have therefore uncovered a mechanism by which synaptic potentiation could alter signal handling by multiple nearby connections.

neuroscience↗

bioRxiv2018

Biophysical underpinning of astroglial physiology probed with realistic cell models

Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+ and generate Ca2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the nanoscopic, sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we have systematically evaluated the multi-scale morphology of protoplasmic astroglia to construct a realistic multi-compartmental cell model that can be biophysically interrogated in NEURON computational environment. This approach has been implemented as an astrocyte-model builder ASTRO. As a proof of concept, we explored a hippocampal astrocyte reconstructed in silico against a battery of physiological and imaging experiments. This exploration has unveiled some basic features of astroglial physiology inaccessible empirically, such as the characteristic length of membrane voltage propagation, membrane effects of local glutamate transport, spatiotemporal dynamics of intracellular K+ redistribution, key Ca2+ buffering properties, and some basic relationships between free Ca2+ dynamics and experimental readout of fluorescent Ca2+ indicators.

neuroscience↗