A method for chronic stimulation of cortical organotypic cultures using implanted electrodes

The neural mechanisms underlying some forms of learning and memory require hours or days to be expressed; however it has proven difficult to study these slowly developing forms of plasticity in reduced preparations due to the short-term nature of acute slice preparations and the fact that most culture preparations lack exposure to structured external input, which plays a critical role in normal cortical development and plasticity. To address this limitation, we developed a method for chronic stimulation of organotypic slice cultures using implanted microelectrodes. This method imparts the ability to apply patterned stimulation to cortical tissue for hours or days, and allows intracellular electrophysiological recordings before and after the stimulation. Importantly, the permanent implantation of the electrodes in the tissue assures that the same neuronal pathways are being excited both during the chronic stimulation while the cultures are in the incubator and while recording in the testing phase. This technique establishes a reduced model for studying experience-dependent plasticity.