Abstract
Gamma-aminobutyric acid (GABA) is critical for proper neural network function and can activate astrocytes to induce neuronal excitability; however, the mechanism by which astrocytes transform inhibitory signaling to excitatory enhancement remains unclear. Computational modeling can be a powerful tool to provide further understanding of how GABA-activated astrocytes modulate neuronal excitation. In the present study, we implemented a biophysical neuronal network model to investigate the effects of astrocytes on excitatory pre- and postsynaptic terminals following exposure to increasing concentrations of external GABA. The model completely describes the effects of GABA on astrocytes and excitatory presynaptic terminals within the framework of glutamatergic gliotransmission according to neurophysiological findings. Utilizing this model, our results show that astrocytes can rapidly respond to incoming GABA by inducing Ca2+ oscillations and subsequent gliotransmitter glutamate release. Elevation in GABA concentrations not only naturally decreases neuronal spikes but also enhances astrocytic glutamate release, which leads to an increase in astrocyte-mediated presynaptic release and postsynaptic slow inward currents. Neuronal excitation induced by GABA-activated astrocytes partly counteracts the inhibitory effect of GABA. Overall, the model helps to increase knowledge regarding the involvement of astrocytes in neuronal regulation using simulated bath perfusion of GABA, which may be useful for exploring the effects of GABA-type antiepileptic drugs.
Highlights
The brain is an adaptive nonlinear dynamic system, in which excitatory-inhibitory (EI) balance is vital for normal brain function [1]
Because this study focused on the regulation of astrocytes on the excitatory neurons, the open proportion U in presynaptic terminal of GABAergic synapse was set a constant for simplification
Numerous in vitro and in vivo studies indicate that astrocytes play a vital role in neuronal excitability and synaptic transmission
Summary
The brain is an adaptive nonlinear dynamic system, in which excitatory-inhibitory (EI) balance is vital for normal brain function [1]. Many reports suggest that elevated GABA concentrations exert both inhibitory and excitatory effects on neuronal firing [11,12,13]. 5 ms τe Excitatory conductance decay time constant 5 ms τi Inhibitory conductance decay time constant 10 ms cyte models [24,25,26], we simplified the model to concentrate only on the IP3-evoked Ca2+ signaling pathway, in which the rate of IP3 production depended on the amount of synaptic glutamate and exogenous GABA in the synaptic cleft. =7s The and an second and third equations describe the production rate of cytoplasmic IP3 induced by exogenous GABA and presynaptic glutamate, respectively. VIgPab a and vIgPlu represent the rate of IP3 production via GABA and glutamate, respectively, and knga1ba and kngl2u are their respective dissociation constants with Hill coefficients n1 and n2.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Computational and Mathematical Methods in Medicine
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
