A role for eCB signaling in synaptic plasticity at the neuronal population level has also been examined. High frequency stimulation (HFS; 5 trains of 100 Hz for 1 second) of the EC induced a long-term potentiation (LTP) of population spike amplitude within the LA (Marsicano et al., 2002). This HFS-induced LTP was significantly enhanced in CB1−/− mice, but not affected by SR141716, suggesting that long-term neural adaptations in these mice could underlie these effects, rather than an acute involvement of eCB signaling. Similarly, LFS (900 pulses at 1 Hz) produced a LTD of population spike amplitude within the LA, which was similar in both wild-type and CB1−/− mice, suggesting no role for eCB signaling in these forms of synaptic plasticity (Marsicano et al., 2002). However, LFS-LTD was prevented by activation of the CB1 receptor specifically located on GABAergic terminals (Azad et al., 2008). Pre-application of either CB1 receptor agonist, Win 55212-2 or THC, prevented LFS-LTD via a mechanisms involving Gi/o proteins, inwardly-rectifying potassium channels, and PKA-dependent regulation of N-type calcium channels. These data provide a novel link between eCB signaling at GABAergic synapses and long-term plasticity at excitatory synapses in the LA (Azad et al., 2008).
