In Vivo Cocaine Experience Generates Silent Synapses

• Published in: Neuron (Cambridge, Mass.) Vol. 63; no. 1; pp. 40 - 47
• Main Authors: Huang, Yanhua H., Lin, Ying, Mu, Ping, Lee, Brian R., Brown, Travis E., Wayman, Gary, Marie, Helene, Liu, Wenhua, Yan, Zhen, Sorg, Barbara A., Schlüter, Oliver M., Zukin, R. Suzanne, Dong, Yan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.07.2009; Elsevier Limited
• Subjects: Animals; Animals, Newborn; Biophysics; Cocaine; Cocaine - pharmacology; Dopamine Uptake Inhibitors - pharmacology; Electric Stimulation - methods; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - genetics; Failure; Gene Expression Regulation - drug effects; Green Fluorescent Proteins - genetics; HUMDISEASE; In Vitro Techniques; Male; Mutation; Neuronal Plasticity - drug effects; Nucleus Accumbens - cytology; Nucleus Accumbens - drug effects; Patch-Clamp Techniques - methods; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - genetics; Receptors, N-Methyl-D-Aspartate - metabolism; Rodents; Synapses - drug effects; Synapses - physiology; SYSNEURO; Transfection; SYSNEURO; HUMDISEASE
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2009.06.007

Studies over the past decade have enunciated silent synapses as prominent cellular substrates for synaptic plasticity in the developing brain. However, little is known about whether silent synapses can be generated postdevelopmentally. Here, we demonstrate that highly salient in vivo experience, such as exposure to cocaine, generates silent synapses in the nucleus accumbens (NAc) shell, a key brain region mediating addiction-related learning and memory. Furthermore, this cocaine-induced generation of silent synapses is mediated by membrane insertions of new, NR2B-containing N-methyl- D-aspartic acid receptors (NMDARs). These results provide evidence that silent synapses can be generated de novo by in vivo experience and thus may act as highly efficient neural substrates for the subsequent experience-dependent synaptic plasticity underlying extremely long-lasting memory.