CC BY
31
XXIII Congress of I.P. Pavlov Physiology Society
ied. The thickness of the sections was 350 |jm, the staining was performed with a calcium indicator Oregon Green 488 BAPTA-1 AM and an astrocytic marker sulforodamine 101. A confocal fluorescence microscope LSM Zeiss 510 DuoScan was used to visualize the calcium events. To analyze the space-time characteristics of calcium dynamics in the network of astrocytes, software was developed on the basis of Matlab, which allowed identifying the space-time characteristics of individual events. The following parameters were investigated: duration of events, maximum projection of events and frequency.
The distribution in accordance with the power law was observed both for the sizes and for the maximum projection of the calcium events. In particular, with ES, a statistically significant increase in the maximum projection was observed, indicating a decrease in the number of large events in comparison with the control. The change in the frequency of events is not statistically significant. This change is pathological in terms of the functioning of the calcium signaling of the astrocytic network.
The work was supported by the Russian Science Foundation (project No. 15-14-30000)
K+ Mediated Signaling within Tripartite Synapse
Alexey Semyanov
Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia.
Living cells had evolved with high intracellular concentration of K+ and with low concentration of Na+. Transmembrane gradients of these ions drive cellular excitability. Therefore, general belief is that K+ efflux is mostly needed for membrane repolarization during action potential. If fact, significant amount of K+ is also released via postsynaptic glutamate receptors during excitatory synaptic transmission in the CNS. This reduces postsynaptic depolarization making synaptic transmission less efficient and more energy costly. Why such K+ permeability is preserved in these receptors? Here, we report that NMDA receptor-dependent K+ efflux can provide a retrograde signal in the synapse. In hippocampal CA3-CA1 synapses, the bulk of astrocytic K+ current triggered by synaptic activity reflects K+ efflux through local postsynaptic NMDA receptors. The local extracellular K+ rise produced by activation of postsynaptic NMDA receptors boosts action potential evoked presynaptic Ca2+ transients and neurotransmitter release from Schaffer collaterals. Perisynaptic K+ accumulation during synaptic transmission also affects astrocytic transporter currents, making them slower. This suggests activity dependent enhancement of glutamate spillover also depends on postsynaptic cell. Our findings indicate that postsynaptic NMDA receptor-mediated K+ efflux contributes to use-dependent synaptic facilitation and increased glutamate dwell time, thus revealing a fundamental form of ionic signaling within tri-partite synapse.
Rapid Astrocyte Morphology Changes Support Epileptic Activity
Stefanie Anders1, Björn Breithausen1, Michel Herde1, Daniel Minge1, Tushar Deshpande1, Anne Boehlen1, Peter Bedner1, Christian Steinhäuser1, Christian Henneberger1,2,3
1 Institute of Cellular Neurosciences, University of Bonn Medical School, Bonn, Germany;
2 Institute of Neurology, University College London, London, United Kingdom;
3 German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Astrocytes actively contribute to neuronal network function. The close contact of individual astrocytes to thousands of neurons enables them to maintain and modulate neuronal function effectively by, for example, buffering potassium and glutamate clearance. A disruption of this spatial relationship could be of pathophysiological significance. Indeed, astrocyte dysfunction and long-term morphology changes have been implicated in numerous diseases including epilepsy. How rapid astrocyte morphology is altered by the onset of epileptiform activity and to what degree it contributes to aberrant network behavior is largely unknown. Combining established protocols of hippocampal epileptogenesis, electrophysiology and two-photon excitation fluorescence microscopy allowed us to monitor astrocyte morphology changes during the induction of epileptiform activity in acute hippocampal slices. Analysis revealed that small and medium-sized astrocyte processes shrink acutely within minutes after epileptiform discharges appeared in the CA1 region. Importantly, similar astrocyte morphology changes were also detected shortly after induction of status epilepticus in vivo by intracerebral kainate injection. In vitro, these astrocyte morphology changes outlasted the induction of epilep-tiform activity, persisted after pharmacological termination of epileptic activity by TTX and were sensitive to inhibition
OM&P
XXIII Congress of I.P. Pavlov Physiology Society
of Rho-associated protein kinase (ROCK, Y-27632). Importantly, ROCK inhibition also reduced epileptiform activity, indicating that rapid astrocyte morphology changes support epileptic activity. A modification of glutamatergic or GAB-Aergic synaptic transmission did not underlie the preconvulsive effect of astrocyte morphology changes. Instead, we observed that intracellular diffusion in astrocytes and diffusion between astrocytes via gap junctions were significantly decreased in parallel to morphology changes. The reduced astrocyte gap junction coupling is likely a consequence of reduced intracellular diffusion because no changes of connexin 43 and 30 expression and phosphorylation were observed. Thus, astrocytes respond to epileptic activity with morphology changes on a time scale of minutes, which reduces intra-and intercellular diffusion in the astrocyte network and supports further epileptic activity. A faster glutamate accumulation, which we detected using the glutamate sensor iGluSnFR after induction of epileptiform activity may link astrocyte remodeling and maintenance of epileptiform activity.
OM&P
Synchronization in Multiplex Glial-Neural Networks
Sergey Makovkin, Mikhail Ivanchenko, Sarika Jalan and Alexey Zaikin
Lobachevsky State University of Nizhni Novgorod, Nizhny Novgorod, Russian Federation;
In work we investigate impact of the glial cells activities on synchronizability of neural cells in multiplex networks framework. Connections among the «glial» cells form a regular star like periodical structure in which each cell is connected to the four other neighbour cells whereas connections, among «neural» cells are represented by an Erdos-Renyi random network with average quantity connections is equal by four.
A multiplex network in which one layer represents interactions among the glial cells and the other layer represents those of neural cells is taken. Connections among the glial cells form a regular star like periodical structure in which each cell is connected to the four other neighbour cells whereas connections, among neural cells are represented by an Erdos-Renyi random network with average quantity connections is equal by four. Inter-layer links are such that each node in the neural layer is connected to its mirror in glial layer and all the four neighbours of the mirror node. The dynamical evolution of the oscillator nodes in this multiplex network is given by the coupled Kuramoto model.
At first case we focus on the case when neural and glial layers are not coupled. Our aim is twofold: we want to capture the effect of network topology on synchronization and study size dependence. The main results in case of uncoupled layers are here:
- Kuramoto order parameter r in neural layer does not depend from layer size and has classical Kuramoto like behaviour ("all-to-all" links).
- In glial layer Kuramoto order parameter strongly depends from layer size: r_glial decrease due to layer size increasing .
- In limit N -> Inf parameter r_glial -> 0, that correspond to 1-D nodes chains (they has no mean field) .
At second case neural and glial layers are coupled. We can conclude several points about synchronization case:
- Mean field in glial layer is born with the interaction of neural layer.
- There is partial desynchronization in glial and neuron layers.
- There is abrupt transition to synchronization.
The work is supported by the RSF (Agreement №. 16-12-00077).
References
1. J. Gardenes, Y. Moreno and A. Arenas Phys. Rev. Lett. 98, 034101 (2007).
2. S. Jalan and A. Singh, 113, 3 (2016).
3. J. Gardenes, Y. Moreno and A. Arenas Phys. Rev. E 75, 066106 (2007).
