Acid-sensing ion channels contribute to synaptic transmission and inhibit cocaine-evoked plasticity
| العنوان: | Acid-sensing ion channels contribute to synaptic transmission and inhibit cocaine-evoked plasticity |
|---|---|
| المؤلفون: | Levi P. Sowers, John A. Wemmie, Yimo Wang, Jianyang Du, Ali Ghobbeh, Rebecca J. Taugher, Caitlin V. Cosme, Yuan Lu, Ryan T. LaLumiere, Collin J. Kreple, Jason J. Radley, Madeliene Stump, Andrea L Schwager-Gutman, Rong Fan, Michael J. Welsh |
| المصدر: | Nature neuroscience |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Male, Dendritic spine, nucleus accumbens, cocaine, Mice, Transgenic, Neurotransmission, Nucleus accumbens, Biology, Synaptic Transmission, Article, Cocaine-Related Disorders, Mice, 03 medical and health sciences, 0302 clinical medicine, Animals, Acid-sensing ion channel, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Neuronal Plasticity, Behavior, Animal, General Neuroscience, Glutamate receptor, Excitatory Postsynaptic Potentials, Neural Inhibition, Rats, Up-Regulation, Associative learning, Mice, Inbred C57BL, Acid Sensing Ion Channels, Disease Models, Animal, ASIC1A, Synaptic plasticity, Excitatory postsynaptic potential, Female, addiction, Neuroscience, 030217 neurology & neurosurgery |
| الوصف: | Acid-sensing ion channel 1A (ASIC1A) is abundant in the nucleus accumbens (NAc), a region known for its role in addiction. Because ASIC1A has been suggested to promote associative learning, we hypothesized that disrupting ASIC1A in the NAc would reduce drug-associated learning and memory. However, contrary to this hypothesis, we found that disrupting ASIC1A in the mouse NAc increased cocaine-conditioned place preference, suggesting an unexpected role for ASIC1A in addiction-related behavior. Moreover, overexpressing ASIC1A in rat NAc reduced cocaine self-administration. Investigating the underlying mechanisms, we identified a previously unknown postsynaptic current during neurotransmission that was mediated by ASIC1A and ASIC2 and thus well positioned to regulate synapse structure and function. Consistent with this possibility, disrupting ASIC1A altered dendritic spine density and glutamate receptor function, and increased cocaine-evoked plasticity, which resemble changes previously associated with cocaine-induced behavior. Together, these data suggest that ASIC1A inhibits the plasticity underlying addiction-related behavior and raise the possibility of developing therapies for drug addiction by targeting ASIC-dependent neurotransmission. |
| اللغة: | English |
| تدمد: | 1546-1726 1097-6256 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7c84c22bf606824c02e188247034cd73 http://europepmc.org/articles/PMC4115047 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....7c84c22bf606824c02e188247034cd73 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15461726 10976256 |
|---|