Figure 1.

Inverse agonist application unmasks persistent CB₁ receptor activity on the axon terminals of perisomatically projecting interneurons. A, Camera lucida reconstruction shows a perisomatically projecting GABAergic interneuron in the CA1 region of the mouse hippocampus. The neuron was filled with biocytin during electrophysiological recording. Although the dendritic tree (red) of this multipolar interneuron covers most hippocampal layers (Ori., stratum oriens; Pyr., stratum pyramidale; Rad., stratum radiatum), its axon arbor (blue) is restricted to the stratum pyramidale, in which somata of CA1 pyramidal neurons are concentrated. Scale bar, 50 μm. Example voltage traces in response to depolarizing and hyperpolarizing current steps (−200 and 150 pA, respectively, from −60 mV) recorded in whole-cell patch-clamp configuration depict spike frequency adaptation typical for CB₁-positive interneurons. Calibration: 30 mV, 0.3 s. Indeed, double-immunofluorescence staining confirms that the biocytin-filled axon terminals (labeled by arrows) of this interneuron contain CB₁ receptors. Scale bar, 10 μm. B–G, Averaged traces of presynaptic action potentials (top) evoked in a perisomatic interneuron and the respective postsynaptic responses (bottom) in CA1 pyramidal cells. Fifty consecutive uIPSCs (gray) and their averages (black) are presented before and during the application of the CB₁ receptor antagonist/inverse agonist AM251 from the same cell pair (10 μm AM251 in B; 1 μm AM251 in E). Note the large increase in uIPSC amplitude and success rate of GABA synaptic transmission after AM251 treatment, indicating the presence of CB₁-dependent tonic signaling at this connection. Summary data showing the proportion of successful transmissions and the euIPSC (including both failures and successes) amplitudes (10 μm AM251 in C, D; 1 μm AM251 in F, G; open circles represent individual pairs; green filled circles label averages). Ctrl, Control.*p < 0.05.