Chronic multichannel recordings from organotypic hippocampal slice cultures: protection from excitotoxic effects of NMDA by non-competitive NMDA antagonists.
In vitro neuronal damage has traditionally been evaluated by biochemical or anatomical but not by electrophysiological techniques. In the present study, we combined two newly developed technologies, an 8 x 8 multi-electrode array (MED-64) and cultured hippocampal slices, to demonstrate the potential use of electrophysiological measures as index of neuronal damage. We first demonstrated the stability of electrophysiological recordings over prolonged periods of time (up to 14 days) in field CA1 of cultured hippocampal slices following electrical stimulation of the Schaffer collateral pathway. We then assessed the neurotoxic properties of NMDA and AMPA and determined that the time-course, potency, and efficacy of these two neurotoxins were similar to those assessed by other experimental approaches. We also compared the efficacy and potency of two non-competitive NMDA receptor antagonists to protect against NMDA-mediated neurotoxicity. Again, the results matched well with the results obtained from traditional techniques. Thus, this new technology might provide a new and powerful method to study the chronic effects of drugs or other experimental manipulations in an in vitro preparation.
Shimono
Ken
K
Tensor Biosciences, 101 Theory Dr, Suite 250, Irvine, CA 92612, USA. kshimono@tensorbio.com
Baudry
Michel
M
Panchenko
Victor
V
Taketani
Makoto
M
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004567:Electrodes, Implanted; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D008559:Memantine / Q000494:pharmacology; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D009435:Synaptic Transmission / Q000187:drug effects; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000633:toxicity
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D008559:Memantine