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IN VITRO ASSESSMENT OF DEVELOPMENTAL NEUROTOXICITY: USE OF MICROELECTRODE ARRAYS TO MEASURE FUNCTIONAL CHANGES IN NEURONAL NETWORK ONTOGENY
Citation:
ROBINETTE, B., W. R. MUNDY, AND T. J. SHAFER. IN VITRO ASSESSMENT OF DEVELOPMENTAL NEUROTOXICITY: USE OF MICROELECTRODE ARRAYS TO MEASURE FUNCTIONAL CHANGES IN NEURONAL NETWORK ONTOGENY. Presented at Society of Toxicology 49th Annual meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
In this study, microelectrode arrays (MEAs) were used to determine if chemical-induced changes in function could be detected by assessing the development of spontaneous network activity.
Description:
Because the Developmental Neurotoxicity Testing Battery requires large numbers of animals and is expensive, development of in vitro approaches to screen chemicals for potential developmental neurotoxicity is a high priority. Many proposed approaches for screening are biochemical, and do not assess function in networks of interconnected neurons. In this study, microelectrode arrays (MEAs) were used to determine if chemical-induced changes in function could be detected by assessing the development of spontaneous network activity. MEAs record individual action potential spikes as well as groups of spikes (bursts) in neuronal networks, and activity can be assessed repeatedly over days in vitro (DIV). Primary cultures of cortical neurons were prepared on MEAs and spontaneous activity was assessed on DIV 2, 6, 9, 13, and 20 to determine the in vitro developmental profile of spontaneous spiking and bursting in cortical networks. In addition 2.5 or 5 pM of the PKC inhibitor bisindolylmaleamide (BIS) was added to MEAs (n= 7-10) on DIV5 to determine if changes in spontaneous activity could be detected in response to inhibition of neurite outgrowth. A clear profile of in vitro activity development occurred in control MEAs, with the number of active channels increasing from O/MEA on DIV2 to 46±5/MEA by DIV13; the rate of increase was most rapid between DIV 6 and 13, and activity declined by DIV 20. A similar pattern was observed for the number of bursting channels, as well as the total number of bursts. BIS caused a concentration-dependent decrease in the number of active channels/MEA, the number of bursting channels/MEA the number of bursts/channel and the number of individual spikes on bursting channels. Other burst characteristics, such as burst duration and the number of spikes in a burst, were unchanged by BIS. These results demonstrate that MEAs can be used to assess the development functional neuronal networks in vitro, as well as chemical-induced dysfunction. (This abstract does not reflect Agency policy