Cannabinoid Receptor Type 1 Located on Presynaptic Terminals of Principal Neurons in the Forebrain Controls Glutamatergic Synaptic Transmission

摘要: It is widely accepted that cannabinoids regulate GABA release by activation of cannabinoid receptor type 1 (CB1). Results obtained from a variety brain regions consistently indicate agonists can also reduce glutamatergic synaptic transmission. However, there are still conflicting data concerning the role CB1 in cannabinoid-induced inhibition transmission cortical areas. Here, we provide direct evidence on terminals principal neurons controls excitatory responses forebrain. In slices basolateral amygdala, CA1 region hippocampus, and primary somatosensory cortex wild-type mice, application agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone (WIN55,212-2; WIN) (5 mum) reduced evoked postsynaptic responses. contrast, conditional mouse mutants lacking all forebrain but not GABAergic interneurons (CB1(f/f;CaMKIIalphaCre)), WIN no longer affected any tested. Compatible with presynaptic mechanism, did change sensitivity to focally uncaged l-glutamate. mice exclusively (CB1(f/f;Dlx5/6-Cre)), thus excluding involvement expressed this effect drug. The present strongly areas directly modulated axon originating neurons.