The Journal of Neuroscience, July 9, 2008, 28(28):7074-7083; doi:10.1523/JNEUROSCI.0899-08.2008
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Development/Plasticity/Repair
Roles of Endocannabinoids in Heterosynaptic Long-Term Depression of Excitatory Synaptic Transmission in Visual Cortex of Young Mice
Yan Huang,1,2
Hiroki Yasuda,3
Abdolrahman Sarihi,1 and
Tadaharu Tsumoto1
1Brain Science Institute, RIKEN, Wako 351-0198, Japan, 2Division of Neurophysiology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan, and 3Education and Research Center, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan
Correspondence should be addressed to Dr. Tadaharu Tsumoto, Brain Science Institute, RIKEN, Wako 351-0198, Japan. Email: tsumoto{at}brain.riken.jp
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.
Key words: developing visual cortex; heterosynaptic LTD; endocannabinoids; BDNF; metabotropic glutamate receptor; LTP
Received Feb. 29, 2008;
revised April 29, 2008;
accepted May 31, 2008.
Correspondence should be addressed to Dr. Tadaharu Tsumoto, Brain Science Institute, RIKEN, Wako 351-0198, Japan. Email: tsumoto{at}brain.riken.jp
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