Journal of Neuroscience Methods 212 (2013) 228–233 Contents lists available at SciVerse ScienceDirect Journal of Neuroscience Methods journa l h omepa g e: www.elsevier.com/locate/jneumeth Basic Neuroscience Slice XVIvo TM : A novel electrophysiology system with the capability for 16 independent brain slice recordings John D. Graef , Haiyang Wei, Patrick M. Lippiello, Merouane Bencherif, Nikolai Fedorov Targacept Inc., Preclinical Research Department, 200 East First Street, Suite #300, Winston-Salem 27101, NC, USA h i g h l i g h t s We designed an electrophysiology system to record from 16 separate brain slices simultaneously. The system is able to obtain stable, extracellular responses from the CA1 region of the hippocampus. The system is able to record NMDA-dependent long-term potentiation. The system can record functional loss and recovery during an oxygen and glucose deprivation insult. The system is both cost- and space-efficient, reduces data variability and minimizes animal use. a r t i c l e i n f o Article history: Received 10 August 2012 Received in revised form 11 October 2012 Accepted 16 October 2012 Keywords: Multi-slice Throughput Field potentials Hippocampus Long-term potentiation Oxygen and glucose deprivation a b s t r a c t Here we validate the design and use of a novel, customized electrophysiology system (Slice XVIvo TM ) that is capable of recording from 16 independent brain slices. The system consists of 16 independent recording chambers in which individual electrodes can be manually manipulated and fixed in order to stimulate and record extracellular responses from 16 brain slices simultaneously. Responses from each brain slice are elicited with individual stimulus isolator units and recorded through separate channels, thus allowing for independent control and analysis of the evoked extracellular activity from each slice. The system was designed to fit on a standard anti-vibration table, thus the Slice XVIvo TM system occupies considerably less space than other currently available multi-slice recording systems. We have demonstrated the utility of the system to obtain stable, extracellular responses from the CA1 region of the hippocampus, as well as induce long-term potentiation. Additionally, we show the utility of the Slice XVIvo TM system to signif- icantly improved throughput for testing compounds in an oxygen and glucose deprivation assay. Overall, we have designed, created and validated a considerably cost- and space-efficient electrophysiology sys- tem that greatly improves throughput while minimizing the number of animals used in experiments. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Electrophysiological recordings from brain slices have been used for over 50 years (Yamamoto and Mcllwain, 1966) and are a critical component for studying the physiology and pharmacology of discrete brain regions and circuits. The slice preparation rep- resents an important cross-functional bridge between in vitro cell culture experiments investigating the function and pharmacology of specific receptors expressed in isolation and in vivo behavioral Abbreviations: ACSF, artificial cerebrospinal fluid; LTP, long-term potentiation; OGD, oxygen and glucose deprivation; DNQX, 6,7-dinitroquinoxaline-2,3-dione; AMPA, 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid; NMDA, N- methyl-d-aspartate. Corresponding author. Tel.: +1 336 462 0642. E-mail address: john@biolucidation.com (J.D. Graef). pharmacology experiments. By maintaining the neuronal and glial architecture within specific brain regions, ex vivo experiments that investigate synaptic function can then be designed to better model neurophysiological activity believed to underlie certain behavioral endpoints within a more physiologically-relevant environment. The brain slice paradigm therefore affords better characterization of novel compounds that have been profiled in in vitro cell cul- ture assays before testing them in expensive and labor-intensive in vivo experiments, thus increasing probability of success as well as reducing animal use. Typical electrophysiology setups for brain slice preparations however, usually only allow for recording from one slice at a time, even though several slices can be cut that contain the brain region of interest. This drawback severely hampers throughput, does not effectively minimize animal use, and can increase variability within a data set due to the day-to-day variations that can occur dur- ing the preparation of brain slices. Recently, a few multi-slice 0165-0270/$ see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jneumeth.2012.10.009