of N40 and D40 iN cells (Fig. 4G). This effect was found to be significantly more robust in D40 versus N40 iN cells in the first minute following DAMGO application. The immediate drop in both AP firing frequency and membrane potential in iN cells suggests that this may be occurring through a G-protein mediated signaling mechanism, which is activated immediately following agonist binding 33. No differences in AP rise time, decay time or half width were detected by DAMGO application (data not shown). However, we observed a slight increase in the after-hyperpolarization potential (AHP) in the D40 versus N40 iN cells (Fig. 4H–I), with no significant difference in firing threshold or AP half width (Fig. 4J–K). These data indicate the functional differences between the two genotypes are at least partly mediated by a preferential decrease in excitability in D40 versus N40 iN cells, likely mediated by alterations in the G-protein coupled signaling cascade. Overall, these data suggest that the DAMGO-induced decrease in excitability is superimposed by a synapse-specific effect, i.e., a stronger reduction in synaptic release probability mediated by presynaptic MOR at the nerve terminal in D40 MOR inhibitory neurons.
