Rationale: Figure 1C,D: Depolarization of CA1 postsynaptic pyramidal neurons mobilizes endocannabinoids, which retrogradely activate presynaptic CB1 receptors, transiently decreasing GABAergic inhibitory neurotransmission (depolarization-induced suppression of inhibition or DSI) or glutamatergic excitatory neurotransmission (depolarization-induced suppression of excitation or DSE). DSI is lost in CB1 knockout mice (Figure 1C,D). Additionally, DSE is lost in CB1 knockout mice (Figure 8A of Ohno-Shosaku, T. et al (2002) J Neurosci, 22(10), 3864-3872).
Figure 3: In addition, evidence is shown that presynaptic N-Type Ca2+ channels are required for endocannabinoid signaling. DSI is occluded by a specific antagonist of N-type channels, ω-conotoxin GVIA, indicating a presynaptic requirement for N-type calcium channels in the regulation of GABAergic transmission by cannabinoids. Conversely, blocking P/Q-type channels results in increased DSI (removes a component of GABA release that is insensitive to DSI and therefore modulation of N-type calcium channels by cannabinoids is now very relevant).. Experimental description: Both mice and rats are used. "Transverse hippocampal slices (300 microns) were obtained from Sprague-Dawley rats (P16-30) or C57BL6J mice."; "CB1+/+, CB1+/- and CB1−/− mice were of both genders and varied in age from 6 weeks to 8 months"