Abstract
Endocannabinoids mediate short- and long-term suppression of synaptic transmission. Nature of presynaptic cannabinoid receptor has been investigated for both excitatory and inhibitory synapses in various regions of the brain. For inhibitory synapses, importance of type 1 cannabinoid receptor (CB1) is generally accepted. For excitatory synapses, however, results are controversial. In the present study, we used electrophysiological and immunohistochemical techniques, and examined the type of cannabinoid receptors functioning at hippocampal and cerebellar excitatory synapses. Using CB1-knockout mice, we demonstrate predominant contribution of CB1 to excitatory synaptic transmission on CA1 pyramidal neurons in the hippocampus and that on cerebellar Purkinje cells from climbing fibers and parallel fibers. The presence of CB1 at presynaptic terminal was confirmed by immunohistochemical experiments with specific antibodies against CB1. In immunoelectron microscopy of the hippocampus and the cerebellar cortex, densities of CB1-positive signal in excitatory terminals were much lower than in inhibitory terminals, but clearly higher than the background level. These results clearly indicate that CB1 is responsible for cannabinoid-dependent suppression of excitatory transmission in the hippocampus and cerebellum. [J Physiol Sci. 2006;56 Suppl:S84]
