Light and electron microscopy of CB1 cannabinoid receptor localization in the rodent hippocampus. (A) CB1 receptor immunostaining with the C-terminus antibody labels a dense axon meshwork in all layers of the hippocampus in CB1+/+ mice. The highest density of CB1-positive SB 525334 is found around the somata of pyramidal cells and at the border of str. pyramidale (sp) and str. radiatum (sr). A subpopulation of interneurons (arrows) are positive for CB1, but pyramidal cells are immunonegative. (B) In contrast, immunostaining for CB1 cannabinoid receptor in CB1−/− mice gave rise to no staining at all, which confirms the specificity of the C-terminus antibody. (C and D) Distal dendrites of pyramidal cells are also innervated by CB1-positive axon terminals (b1), in addition to the somata and proximal dendrites (not shown), as illustrated in serial sections from the border of str. radiatum and str. lacunosum-moleculare. Silver–gold particles (small arrows) depicting the CB1 receptors were found on axon terminals making symmetrical (mostly GABAergic) synapses (arrowhead). In contrast, axon terminals (b2) forming asymmetrical (mostly glutamatergic) synapses (arrows) on spine heads are avoided by silver–gold particles, and are therefore considered CB1-negative. Abbreviations: so, stratum oriens; sp, stratum pyramidale; sr, stratum radiatum; slm, stratum lacunosum-moleculare. Scale bars: 80 μm (for A and B) and 0.2 μm (for C and D), respectively.