The role of protein synthesis in striatal long-term depression.
Long-term depression (LTD) at the corticostriatal synapse is postsynaptically induced but presynaptically expressed, the depression being a result of retrograde endocannabinoid signaling that activates presynaptic cannabinoid CB1 receptors and reduces the probability of glutamate release. To study the role of protein synthesis in striatal LTD, we used a striatum-only preparation in which the presynaptic cell body is cut off, leaving intact only its axons, whose terminals synapse on medium spiny neurons. LTD (duration >150 min) was induced in this preparation, thus providing evidence that transcription in the presynaptic cell nucleus is not necessary for this form of plasticity. The maintenance of striatal LTD, however, was blocked by bath application of protein translation inhibitors but not by the same inhibitors loaded into the postsynaptic cell. These results suggest that local translation is critical for the expression of striatal LTD, distinguishing this form of mammalian synaptic plasticity from other forms that require postsynaptic protein synthesis. Possible roles of axonal or glial translation in striatal LTD are considered.
Yin
Henry H
HH
Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892, USA.
Davis
Margaret I
MI
Ronesi
Jennifer A
JA
Lovinger
David M
DM
D000344:Afferent Pathways / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D003342:Corpus Striatum / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D063385:Cannabinoid Receptor Modulators; D009419:Nerve Tissue Proteins; D011500:Protein Synthesis Inhibitors; D043884:Receptor, Cannabinoid, CB1; D018698:Glutamic Acid; D003513:Cycloheximide