In addition to the modulation of IPSCs by direct CB1 receptor activation, eCB signaling has been demonstrated to mediate long-term depression (LTDi) and depolarization-induced suppression (DSI) of inhibitory synaptic transmission onto principal neurons of the BLA. Initial studies by Marsicano et al., within the BA, showed that LTDi was induced by low frequency (1 Hz) stimulation (LFS) of the external capsule (100 pulses), which produced a decrease in isolated GABA-A receptor-mediated eIPSC amplitude to 66% of control. This reduction in IPSC amplitude was accompanied by an increase in the PPR, indicating a presynaptic expression mechanism. In addition, LFS reduced sIPSC frequency but not amplitude, further suggesting a presynaptic mechanism of action (Azad et al., 2004). Furthermore, LFS-induced LTDi was mediated by eCB signaling, as it was absent in CB1−/− mice and prevented by the CB1 receptor antagonist SR141716.
