P226 Astrocyte modulation of neural oscillations: mechanisms underlying slow wave activity in cortical networks
Thiago Ohno Bezerra*1, Antonio C. Roque1
1Department of Physics, School of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
*Email: thiagotakechi@usp.br
Introduction
Oscillatory activity plays a pivotal role in neural networks. Astrocytes have recently been shown to modulate neural activity through the release of glutamate and ATP, the latter acting as an inhibitory neuromodulator, and have been implicated in the regulation of slow cortical oscillations, specifically the up and down states observed in these networks. However, the mechanisms by which astrocytes influence neural oscillations and shape network activity remain poorly understood.
Methods
We extended the INEXA model [1] to incorporate the adaptation of neural activity. Neurons (N = 250) and astrocytes (N = 75, 30% of neurons) are randomly distributed in a 3D volume (750 × 750 × 10 µm3). Each neuron is modeled as a stochastic unit, where its spiking probability depends on neural excitatory and inhibitory inputs, ATP-mediated inhibition from astrocytes, an adaptive variable (u), and background noise (c = 0.03). The variable u increases after each neuronal spike and decays over time. Presynaptic neuron activity enhances IP3concentration in astrocytes, which elevates local Ca2+levels. Astrocyte activity is modeled as a stochastic process, driven by local Ca2+responses and the activation of neighboring astrocytes. Glutamate release from astrocytes promotes synaptic facilitation, influencing neuron-to-neuron communication. Connectivity between neurons and astrocytes is governed by a probabilistic rule based on spatial proximity.
Results
The model predicts that without astrocytes, neural networks oscillate at frequencies that vary according to the increment and decay rates of the variable u. These oscillations show no slow-wave patterns. In contrast, when astrocytes are included, the network exhibits three distinct activity modes: (1) high-frequency asynchronous spiking, (2) alternating between high-frequency spiking and silent states, and (3) regular synchronous spiking. The second mode, characterized by alternating states, is particularly reminiscent of cortical up and down states associated with slow oscillations. The specific mode of activity is influenced by the dynamics of the adaptive variable u, which modulates the frequency and pattern of oscillations. Astrocytic synaptic potentiation, ATP-mediated inhibition, and astrocyte activation duration also regulate the slow oscillation frequency.
Discussion
Our results suggest that astrocytes play an integral role in modulating the activity patterns of neural networks. Through the release of glutamate and ATP, astrocytes influence both excitatory and inhibitory processes, thereby altering network dynamics. These findings support the hypothesis that astrocytes are essential for the generation and regulation of slow oscillations in cortical networks, specifically in the context of up and down states. The modulation of these oscillations by astrocytic activity may provide a mechanism through which astrocytes influence cognitive processes associated with neural synchrony.
Acknowledgements
This work was produced as part of the activities of FAPESP Research, Innovation and Dissemination Center for Neuromathematics (grant 2013/07699-0). TOB is supported by a FAPESP PhD scholarship (grant 2021/12832-7, BEPE: 2024/14422-9). ACR is partially supported by a CNPq fellowship (grant 303359/2022-6).
References
[1] Lenk, K., Satuvuori, E., Lallouette, J., Ladrón-de-Guevara, A., Berry, H., & Hyttinen, J. A. (2020). A computational model of interactions between neuronal and astrocytic networks: The role of astrocytes in the stability of the neuronal firing rate. Frontiers in Computational Neuroscience, 13, 92. https://doi.org/10.3389/fncom.2019.00092
