Unique inhibitory synapse with particularly rich endocannabinoid signaling machinery on pyramidal neurons in basal amygdaloid nucleus

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 7; pp. 3059 - 3064
• Main Authors: Yoshida, Takayuki, Uchigashima, Motokazu, Yamasaki, Miwako, Katona, Istvan, Yamazaki, Maya, Sakimura, Kenji, Kano, Masanobu, Yoshioka, Mitsuhiro, Watanabe, Masahiko
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 15.02.2011; National Acad Sciences
• Subjects: Amygdala; Amygdala - cytology; Animals; Arachidonic Acids - metabolism; Behavioral neuroscience; Biological Sciences; Brain; Cannabinoid CB1 receptors; Cannabinoid Receptor Modulators - metabolism; Cholecystokinin; Cholecystokinin - metabolism; Convergence; Data processing; Depolarization; Electrophysiology; Endocannabinoids; Excitability; Extinction; gamma -Aminobutyric acid; Gene expression; Glycerides - metabolism; Immunohistochemistry; In Situ Hybridization, Fluorescence; Interneurons; Invaginations; Lipoprotein lipase; Lipoprotein Lipase - genetics; Lipoprotein Lipase - metabolism; Membranes; Memory; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Confocal; Microscopy, Electron; Microscopy, Immunoelectron; Monoacylglycerol Lipases - metabolism; Nerve endings; Neural Inhibition - physiology; Neurons; Neurotransmitter release; Neurotransmitters; Presynapse; Proteins; Pyramidal cells; Pyramidal Tracts - metabolism; Receptors; Signal transduction; Signal Transduction - physiology; Synapses; Synapses - metabolism; Synapses - physiology; synaptic depression; Synaptic Transmission - physiology; Triacylglycerol lipase
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1012875108

2-Arachidonoylglycerol (2-AG) is the endocannabinoid that mediates retrograde suppression of synaptic transmission in the brain. 2-AG is synthesized in activated postsynaptic neurons by sn-1-specific diacylglycerol lipase (DGL), binds to presynaptic cannabinoid CB₁ receptors, suppresses neurotransmitter release, and is degraded mainly by monoacylglycerol lipase (MGL). In the basolateral amygdala complex, it has been demonstrated that CB₁ is particularly enriched in axon terminals of cholecystokinin (CCK)-positive GABAergic interneurons, induces short- and long-term depression at inhibitory synapses, and is involved in extinction of fear memory. Here, we clarified a unique molecular convergence of DGLα, CB₁, and MGL at specific inhibitory synapses in the basal nucleus (BA), but not lateral nucleus, of the basolateral amygdala. The synapses, termed invaginating synapses, consisted of conventional symmetrical contact and unique perisynaptic invagination of nerve terminals into perikarya. At invaginating synapses, DGLα was preferentially recruited to concave somatic membrane of postsynaptic pyramidal neurons, whereas invaginating presynaptic terminals highly expressed CB₁, MGL, and CCK. No such molecular convergence was seen for flat perisomatic synapses made by parvalbumin-positive interneurons. On the other hand, DGLα and CB₁ were expressed weakly at axospinous excitatory synapses. Consistent with these morphological data, thresholds for DGLα-mediated depolarization-induced retrograde suppression were much lower for inhibitory synapses than for excitatory synapses in BA pyramidal neurons. Moreover, depolarization-induced suppression was readily saturated for inhibition, but never for excitation. These findings suggest that perisomatic inhibition by invaginating synapses is a key target of 2-AG-mediated control of the excitability of BA pyramidal neurons.