Self-administering neuronal networks

Summary form only given. Dissociated hippocampal neurons form complex networks and spontaneously produce action potentials during their development in vitro: eventually establishing patterns of tightly-bound global electrical activity. This highly synchronous epileptiform-like activity is considered pathological and provides a model of seizures both in vivo and in vitro. We have developed a closed-loop drug-delivery system, in which the firing activity of cultured neuronal networks is used to control a syringe pump. This allows the network to self-administer pharmacological agents to modulate its own electrical state. Rat embryonic hippocampal cells cultured on 60-channel multielectrode arrays (MEA), were recorded at 7 day intervals to examine morphological and electrical development; before treatment with 0.3μM of the GABA antagonist bicuculline at 28 div. Complex morphological networks had formed in cultures by 7 div, with spontaneous electrical activity apparent by day 14. Global epileptiform-like activity was established between 21 and 28 div, and was intransigent to modulation with 0.3μM bicuculline. This system will be expanded to integrate the network with an optical stimulation system. Further pharmacological investigations during early development of neuronal cultures, and implementation of the self-administration system with the aim of encouraging or discouraging particular network states, are planned.