eCB signaling has also been explored at the circuit level in vitro. Specifically, eCB-mediated LTDi (see details above) is expected to increase the excitability of BLA projection neurons by decreasing inhibitory tone, and thus increase the activity of BLA target neurons in the CeA, nucleus accumbens, and prefrontal cortex. Using extracellular field potential recordings, Azad et al. found that high frequency stimulation (100 pulses 50 Hz, HFS) of the external capsule (EC) produced a long-term potentiation (LTP) of field potentials recorded from the BLA (Azad et al., 2004). Interestingly, pre-induction of LTDi enhanced the magnitude of HFS-induced LTP; an effect that was abolished by the CB1 receptor antagonist SR141716. To determine whether this enhanced excitability of BLA neurons in response to eCB-mediated LTDi affects the activity of their target neurons, EPSCs from neurons within the CeA were recorded in response to LA stimulation, before and after HFS-LTP induction. Pre-induction of eCB-dependent LTDi enhanced LTP in the LA-CeA pathway, an effect abolished by SR141716 (Azad et al., 2004). These findings suggest eCB-mediated LTDi enhances the excitability of BLA neurons in response to afferent stimulation and thus, increases the activity of the BLA-CeA pathway.
