CC BY
17
XXIII Congress of I.P. Pavlov Physiology Society
Interactive Realistic Model of Protoplasmic Astrocyte
L. P. Savtchenko*1, C. Henneberger*1,2,3, L. Bard*1, T. P. Jensen1, J. P. Reynolds1, I. Kraev4, M. Medvedev4, M. G. Stewart4, D. A. Rusakov1
1 UCL Institute of Neurology, University College London, UK;
2 Institute of Cellular Neuroscience, University of Bonn, Germany;
3 German Center of Neurodegenerative Diseases, Bonn, Germany;
4 The Open University, Milton Keynes, UK.
Electrically non-excitable astrocytes appear able in transducing, integrating and propagating physiological intracellular diffusion signals. Decrypting this type of signalling, however, poses a conceptual difficulty because it requires an understanding of molecular interactions in the massive morphological structure of nanoscale-thin leaf-like processes which constitute the bulk of astrocyte geometry. How a particular cell signalling engages a precise type of geometry remains therefore poorly understood.
There have been no attempts to develop an astrocyte model with such a spongy morphology even though this could provide the key to mechanistic insights into astrocytic physiology and Ca2+ signalling.
To understand the role of complex pattern in cell function we have adapted the NEURON modelling environment to build a simulation tool to produce different astrocyte models with the detailed morphology, membrane properties and known molecular signalling mechanisms. The tool enables to design a distributed Ca2+ homoeostasis mechanisms including diffusion, wave propagation, gap-junction escape or channel currents whereas the simulation environment also has the capability to mimic uncaging, membrane physiology, volume current injections or fluorescence recovery after photobleaching (FRAP) experiments in the 3D tissue volume containing the astrocyte.
In our illustration study, the tool generates astrocyte which has adapted the features of hippocampal protoplasmic astrocytes (area CA1) documented through a combination of experiments involving electrophysiology, two-photon excitation imaging, a FRAP super-resolution technique and quantitative electron microscopy. We demonstrate how simulations with the model could help to unveil some fundamental features of astrocytic morphology and Ca2+ signalling that are not accessible to direct experimental probing.
To our knowledge, this is the first attempt to have a full-scale tool for astroglia simulations, which we believe will attract significant interest among a broad audience of cell biologists and neuroscientists.
Modeling of Neural Networks with Tetrapartite Synapses
S.V.Stasenko1*, I.A.Lazarevich1, V.B.Kazantsev1, A.E. Dityatev1,2
1 Lobachevsky university (UNN), Russia;
2 German Center for Neurodegenerative Diseases, Magdeburg, Germany. * Presenting e-mail: stasenko@neuro.nnov.ru
Uncovering the key role of different brain cells and structures in information processing and health and disease is the main task of modern neuroscience. Many years neurons were considered as the key players in information processing. Recent experimental study has uncovered crucial role in information processing of extracellular matrix molecules and astrocytic cells activity [1-4] . The neuron-glial interaction is mediated by spillover (diffusion) of neurotransmitters in the extracellular space and their binding to astrocytic membrane receptors. For example, released D-serine and ATP from astrocyte after binding of neurotransmitter to astrocytic membrane receptors might induce currents through ionotropic receptors on the postsynaptic side as well as lead to long-term changes through activation of metabotropic receptors. Activation of kainite receptors by astrocytic glutamate induces axonal depolarization and reduction of AP generation threshold, and hence changes the properties of spontaneous IPSCs, namely increases their frequency and amplitude [3]. In a series of experimental investigation, the role of extracellular matrix (ECM) molecules in regulation of synaptic transmission and neuronal excitability was highlighted. It is assumed that ECM-mediated regulation mechanisms are involved in homeostatic modulation of neuronal activity on extended time scales [1,2]. ECM-induced homeostatic plasticity helps prevent the pathological hypo- and hyper-excitation of neurons which may cause dysfunction and cell death. For instance, an experimentally observed effect referred to as synaptic scaling helps neurons maintain the extent of their activity within a certain range under different inputs [5,6]. Besides the neuron-glial and ECM-neuron interaction pathways there also exists ECM-astrocyte interaction which format the structure in the brain - tetrapartite synapse . Activation of glial cells is not only elicited by the diffusing neurotransmitter, but also by ECM
OM&P
10 Opera Med Physiol 2017 Vol. 3 (S1)
