title: Roles of endocannabinoids in heterosynaptic long-term depression of excitatory synaptic transmission in visual cortex of young mice.
abstract: Tetanic stimulation of one of two afferent pathways converging to neurons in the visual cortex induces long-term depression (LTD) of synaptic transmission in the other, nonactivated pathway under a certain condition. This form of synaptic plasticity called heterosynaptic LTD (hetero-LTD) was not systematically investigated in previous studies, whereas homosynaptic LTD has been extensively studied. To determine whether hetero-LTD is induced in visual cortical slices of mice and, if so, through what mechanisms, we recorded EPSPs evoked in layer II/III neurons by alternating test stimulation of two sites in layer IV at 0.05 Hz. After theta-burst stimulation of one site, EPSPs evoked by test stimulation of the other site were depressed for a long time in most of the neurons, whereas homosynaptic long-term potentiation was induced at activated synapses. Such a hetero-LTD was induced in most mice at postnatal day 7-20 (P7-P20), but not induced in mice at P35-P41. Tests using the paired-pulse stimulation protocol and coefficient of variation analysis suggested that hetero-LTD was expressed at presynaptic sites. Pharmacological analysis indicated that this form of LTD was induced through activation of the type 5 of metabotropic glutamate receptors, not through the NMDA type of glutamate receptors. Additional analysis using a cannabinoid type 1 receptor agonist and an antagonist suggested that endocannabinoids (eCBs) are involved in this type of LTD. Moreover, results suggest that brain-derived neurotrophic factor, which may be released from strongly activated presynaptic sites, prevents eCBs from suppressing the release of transmitters from these sites.
authors.affiliation: Brain Science Institute, RIKEN, Wako 351-0198, Japan.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yasuda
authors.forename: Abdolrahman
authors.initials: A
authors.lastname: Sarihi
authors.forename: Tadaharu
authors.initials: T
authors.lastname: Tsumoto
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D063388:Endocannabinoids; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology* / Q000528:radiation effects; D007074:Immunoglobulin G / Q000494:pharmacology; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000502:physiology* / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D020813:Receptor, trkB / Q000276:immunology; D014793:Visual Cortex / Q000166:cytology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D018683:Excitatory Amino Acid Agents; D007074:Immunoglobulin G; D010880:Piperidines; D011720:Pyrazoles; C103505:AM 251; D020813:Receptor, trkB; D002118:Calcium