Zhu and Lovinger have also demonstrated a role for eCB signaling in DSI at inhibitory synapses onto BLA principal neurons in mechanically dissociated postsynaptic neuron/synaptic bouton preparations and in acute rat brain slices (Zhu and Lovinger, 2005). In the acute brain slice preparation, post-synaptic depolarization (−60 to 0 mV) of BLA principal neurons for 4 seconds produced a 44% decrease in sIPSC frequency and a 34% decrease in sIPSC amplitude. Chelation of postsynaptic calcium eliminated DSI, however, a slowly developing decrease in sIPSC frequency was still present under these conditions. The mGluR5 receptor antagonist MPEP did not eliminate DSI but did significantly shorten its duration, suggesting that the longer-lasting component of DSI requires mGluR5 receptor activation, rather than increases in intracellular calcium (Zhu and Lovinger, 2005). These data further suggest that mGluR-dependent long-term eCB-mediated depression of GABAergic transmission is calcium independent.
