Analysis of Network Level Effects
of the Compound Trimethylopropane Phosphate (TMPP)
This work was preformed at the University of
California at Irvine
Goal: To develop the multi-electrode system as a
tool for detecting and defining neurotoxins and more specifically the neurotoxin
TMPP.
Progress: Figure 1 summarizes a typical experiment plotting
the distribution of responses evoked by single pulse stimulation to the
Schaffer-commissural projections at the noted site. As is evident, 2 µM
concentration of TMPP caused the single pulse to trigger reverberating
activity beginning at about 10 msec. The center of this activity appears
to be in the cell bodies and proximal apical dendrites of field CA3 b;
this point is being confirmed with current source density analysis. This
pattern is similar to that produced by antagonists of the GABAa receptor,
and in good agreement with the results obtained at USC. A second and less
obvious effect is a suppression of the monosynaptic EPSPs in fields CA3
and especially CA1. If confirmed with additional experiments, this result
points to a further and unexpected effect of the compound that is not likely
to be related to GABA receptors. It is also evident from the figure that
2 µM concentrations are well above threshold; work is now being carried
out with lower concentrations.
Figure 2 shows that TMPP first slows the hippocampal
EEG and then causes it to become desynchronized. The latter, delayed change
is in accord with an action on GABAa receptors; the more rapid, presumably
lower threshold slowing of the EEG points to some other type of mechanism.
These points should be clarified by experiments using submicromolar concentrations
of the toxin.
Figure 2: Effect of TMPP on EEG activity recorded
at various sites of hippocampal slice culture.