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Alteration of network activity in cortical neurons by triadimefon
Citation:
Lynch, B., C. Mack, AND Tim Shafer. Alteration of network activity in cortical neurons by triadimefon. Society of Toxicology, San Diego, CA, March 22 - 27, 2015.
Impact/Purpose:
To be presented at the annual 2015 SOT
Description:
ABSTRACT BODY: Triadimefon (TRI) is a conazole fungicide used to control powdery mildews on crops and as a veterinary and clinical treatment. TRI inhibits transmitter re-uptake at dopaminergic synapses in the central nervous system, and exposure to high levels of TRI causes hyperactivity and repetitive behavior. Recently, we reported that other conazole fungicides similar to TRI decreased spontaneous electrical activity in cortical cultures grown on microelectrode arrays (MEAs). The present experiments used MEAs to assess effects of TRI on spontaneous network activity by measuring the mean firing rate (MFR) of action potentials (spikes), bursting (groups of spikes) parameters, and synchrony of bursts (SYNC) in primary cortical cell cultures from neonatal (0-24h old) rats. Stable native activity from mature networks (n=11) was recorded for 30 mins (BL) prior to exposure of TRI (0.01-100 µM) via a cumulative concentration paradigm. TRI (0.5-100 µM) decreased MFR in a concentration-dependent manner (EC50 =7.9 µM).TRI increased burst parameters, including the interburst interval, %spikes/burst and burst duration. Most notably, TRI caused a U-shaped change in SYNC, which first decreased (0.01-0.5 uM) by 46 %, then recovered to control levels (1-100 uM). TRI yielded a unique array of effects on cortical function that require additional study to ascertain the exact mechanisms involved. (This abstract does not reflect U.S. EPA policy.)