P298 The important role of astrocytic Na+ signaling in the astrocyte-neuron communication
Pawan K Thapaliya1, Alok Bhattarai1, and Ghanim Ullah1,* 1Department of Physics, University of South Florida, Tampa, FL 33620, USA. *Email: gullah@usf.edu
Introduction
Emerging evidence indicates that neuronal activity-evoked changes in Na+concentration in astrocytes ([Na]a)represent a special form of excitability, which is tightly linked to all other major ions in the astrocyte and extracellular space, as well as to bioenergetics, neurotransmitter uptake, and neurovascular coupling. Furthermore, [Na]aexhibits significant heterogeneity at the subcellular, cellular, and brain region levels.
Methods We develop biophysical models to determine how [Na]acan regulate astrocytic function. We further investigate what does the spatial heterogeneity of [Na]aat different scales mean for the astrocyte-neuron communication. Our models are supported by extensive data imaging Na+ signals in astrocytes under different conditions. Results Our work highlights the importance of [Na]ain almost every aspect of astrocytic function. For example, we have shown that the observed brain-region specific heterogeneity in [Na]asignaling leaves cortical astrocytes more susceptible to Na+and Ca2+overload under metabolic stress as compared to hippocampal astrocytes. The model also predicts that activity-evoked [Na]atransients result in significantly higher ATP consumption in cortical astrocytes than in the hippocampus. The difference in ATP consumption is mainly due to the different expression levels of NMDA receptors in astrocytes in the two brain regions [1]. The model also closely reproduces the dynamics of extra- and intracellular pH under different conditions [2]. Furthermore, in conjunction with experimental data our models also reveal that Na+ concentration varies across the cellular compartments, from one cell to another, and across brain regions.
Discussion Overall, this study emphasizes the significance of incorporating Na+ homeostasis in computational models for neuro-astrocytic coupling, specifically when studying brain (dys)function under metabolic stress. Our study also highlights that by using different Na+concentrations, how different astrocytes can differentially regulate the function of different neurons or different synapses emanating from the same neuron.
Acknowledgements This work is supported by the National Institutes of Health through grant number R01NS130916. References [1] Thapalia P, Pape N, Rose CR, and Ullah G (2023), Modeling the heterogeneity of sodium and calcium homeostasis between cortical and hippocampal astrocytes and its impact on bioenergetics, Front. Cell. Neurosci., 17, 1035553.
[2]Everaerts K, Thapaliya P, Pape N, Durry S, Eitelmann S, Ullah G, and Rose CR (2023), Inward Operation of Sodium-Bicarbonate Cotransporter 1 Promotes Astrocytic Na+ Loading and Loss of ATP in Mouse Neocortex during Brief Chemical Ischemia, Cells, 12, 2675.
