Figure 1. Depression of excitatory transmission to striatal MSNs by postsynaptic loading of the 2-AG precursor SAG.

(a) EPSC amplitudes are plotted from a representative individual cell loaded with SAG. The shaded regions labeled as 1 and 2 correspond to the baseline and post-treatment periods respectively. (b) Compilation of data from cells loaded with Vehicle (100±9% baseline), SAG (102±6% baseline) and SAG loaded in the presence of DHPG (10 µM; 132±19% baseline) at −80 mV showing no depression in any group (p>0.05 by one-sample t-test comparing to 100%). There is no significant difference between groups as determined by 2-way repeated measures ANOVA. Representative traces averaged over the 1^st and 2^nd periods shown in the shaded regions of panel (a) are shown (1: black trace; 2: gray trace, scale bars 100 pA, 10 ms). (c) SAG loading did not affect PPR in MSNs voltage-clamped at −80 mV (p>0.05 by paired t-test). (d) EPSC amplitudes are plotted from representative cells loaded with SAG or vehicle at −50 mV. (e) Compilation of data from cells loaded with SAG at −50 mV (SAG) showing a progressive and significant depression of EPSC amplitudes (68±3% baseline; p<0.0001 by one-sample t-test), whereas vehicle-loaded cells were unaffected (102±6% baseline). Analysis using a 2-way repeated measures ANOVA revealed a significant interaction between SAG and Vehicle loaded cells with Sidak’s Posthoc showing significantly different normalized amplitudes as indicated (** p<0.01, *** p<0.001, **** p<0.0001). (f) SAG loading significantly increased PPR at −50 mV (* p<0.05 by paired t-test).