Abstract

Neuronal hyperexcitation, a hallmark of various neurological disorders, is often linked to dysregulated membrane excitability and synaptic transmission. This study investigates the potential of cannabinoid receptor activation to modulate pathological network activity in the hippocampus, a brain region critical for learning and memory. Using multielectrode array (MEA) recordings on cultured rat hippocampal slices, we examined the effects of a non-selective cannabinoid receptor agonist on spontaneous and induced epileptiform activity. Our objective was to determine if the activation of these G-protein coupled receptors, which are integral to the cell membrane, could restore network homeostasis. The results demonstrate that the application of the agonist significantly reduced the frequency and amplitude of synchronized burst discharges, a proxy for hyperexcitation, in a dose-dependent manner. This suppression suggests a potentiation of inhibitory signaling or a direct modulation of voltage-gated ion channels, highlighting the critical role of membrane-associated cannabinoid receptors in regulating neuronal network stability. These findings provide compelling evidence for the therapeutic potential of targeting the endocannabinoid system to manage conditions characterized by neuronal hyperexcitability, offering a novel avenue for pharmacological intervention in cell and membrane biology.