Abstract
Astrocytes and neurons respond to each other by releasing transmitters, such as γ-aminobutyric acid (GABA) and glutamate, that modulate the synaptic transmission and electrochemical behavior of both cell types. Astrocytes also maintain neuronal homeostasis by clearing neurotransmitters from the extracellular space. These astrocytic actions are altered in diseases involving malfunction of neurons, e.g., in epilepsy, Alzheimer’s disease, and Parkinson’s disease. Convulsant drugs such as 4-aminopyridine (4-AP) and gabazine are commonly used to study epilepsy in vitro. In this study, we aim to assess the modulatory roles of astrocytes during epileptic-like conditions and in compensating drug-elicited hyperactivity. We plated rat cortical neurons and astrocytes with different ratios on microelectrode arrays, induced seizures with 4-AP and gabazine, and recorded the evoked neuronal activity. Our results indicated that astrocytes effectively counteracted the effect of 4-AP during stimulation. Gabazine, instead, induced neuronal hyperactivity and synchronicity in all cultures. Furthermore, our results showed that the response time to the drugs increased with an increasing number of astrocytes in the co-cultures. To the best of our knowledge, our study is the first that shows the critical modulatory role of astrocytes in 4-AP and gabazine-induced discharges and highlights the importance of considering different proportions of cells in the cultures.
Highlights
Astrocytes are glial cells that control and sustain homeostasis in the central nervous system (CNS)
The following sections present the results obtained by live/dead assays, the cell counting of the different cell cultures, the spike rate (SR) and burst rate (BR) analyses of the baseline activities due to AP and gabazine stimulation, and the analysis of the synchronization based on cross-correlations and the binned spiking activity
We aimed to investigate how astrocytes may play a role in the regulation of neuronal activity during drug-induced epileptiform behavior
Summary
Astrocytes are glial cells that control and sustain homeostasis in the central nervous system (CNS). We aim to investigate the role of astrocytes in the homeostasis of neuronal activity after the application of commonly used chemicals to induce epileptiform behavior. GJs maintain brain functions, e.g., by channeling the propagation of adjoining astrocytic calcium (Ca2+ ) waves and regulating ion flow, neuronal activity, and behavior [1]. The interconnected group of a pre- and post-synaptic neuron and the astrocyte is referred to as tripartite synapse [2]. When glutamate binds to the metabotropic glutamate receptors (mGluRs) at the astrocytic cell membrane, a cascade of chemical reactions elicits inositol trisphosphate (IP3 ) production, which triggers intracellular [Ca2+ ]i transients [5]. The role of GABAA in astrocytes is still unclear; previous research reported that GABAA receptor (GABAA R)
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