Toxicological testing: Effects of TMPP on Network Activity

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  Goal: To establish the effects of Trimethylopropane phosphate (TMPP) (a neurotoxin formed during partial pyrolysis of certain synthetic lubricants or flame retardant polyurethane foams) on network activity.    Progress: We used the multi-electrode array (MEA) to monitor the effects of TMPP on the spatio-temporal electrophysiological properties of rabbit and rat hippocampus in vitro. Properties evaluated included mono- and multi-synaptic activation, paired-pulse facilitation and high frequency stimulation-induced LTP. TMPP (20 µM) increased the amplitude of EPSPs after a delay of approximately 15 s and led to an increase in the amplitude of population spikes (Fig. 1) An increase in the number of population spikes evoked by each impulse also was observed. High concentrations of TMPP induced spontaneous electrical activity which included spike bursting. TMPP also was tested on dissociated hippocampal cells cultured on an electrode array. Application of TMPP produced an increase in the spontaneous firing rate. These results are consistent with the known seizure-inducing effects of TMPP, possibly due to an agonistic effect at GABAa receptors.  

 

Figure 1:Effect of TMPP on evoked electrical activity in acute rat hippocampal slices recorded with the MEA 1060 multielectrode array.