Delta opioid receptors engage multiple signaling cascades to differentially modulate prefrontal GABA release with input and target specificity
Summary: Opioids regulate circuits associated with motivation and reward across the brain. Of the opioid receptor types, delta opioid receptors (DORs) appear to have a unique role in regulating the activity of circuits related to reward without liability for abuse. In neocortex, DORs are expressed p...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725000646 |
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| author | Ryan P.D. Alexander Kevin J. Bender |
| author_facet | Ryan P.D. Alexander Kevin J. Bender |
| author_sort | Ryan P.D. Alexander |
| collection | DOAJ |
| description | Summary: Opioids regulate circuits associated with motivation and reward across the brain. Of the opioid receptor types, delta opioid receptors (DORs) appear to have a unique role in regulating the activity of circuits related to reward without liability for abuse. In neocortex, DORs are expressed primarily in interneurons, including parvalbumin- and somatostatin-expressing interneurons that inhibit somatic and dendritic compartments of excitatory pyramidal cells, respectively. But how DORs regulate transmission from these key interneuron classes is unclear. We found that DORs regulate inhibition from these interneuron classes using different G-protein signaling pathways that both converge on presynaptic calcium channels but regulate distinct aspects of calcium channel function. This imposes different temporal filtering effects, via short-term plasticity, that depend on how calcium channels are regulated. Thus, DORs engage differential signaling cascades to regulate inhibition depending on the postsynaptic target compartment, with different effects on synaptic information transfer in somatic and dendritic domains. |
| format | Article |
| id | doaj-art-d1e72d8015aa48cba27cfcd7be03be23 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-d1e72d8015aa48cba27cfcd7be03be232025-02-10T04:34:19ZengElsevierCell Reports2211-12472025-02-01442115293Delta opioid receptors engage multiple signaling cascades to differentially modulate prefrontal GABA release with input and target specificityRyan P.D. Alexander0Kevin J. Bender1Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA; Corresponding authorWeill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA; Corresponding authorSummary: Opioids regulate circuits associated with motivation and reward across the brain. Of the opioid receptor types, delta opioid receptors (DORs) appear to have a unique role in regulating the activity of circuits related to reward without liability for abuse. In neocortex, DORs are expressed primarily in interneurons, including parvalbumin- and somatostatin-expressing interneurons that inhibit somatic and dendritic compartments of excitatory pyramidal cells, respectively. But how DORs regulate transmission from these key interneuron classes is unclear. We found that DORs regulate inhibition from these interneuron classes using different G-protein signaling pathways that both converge on presynaptic calcium channels but regulate distinct aspects of calcium channel function. This imposes different temporal filtering effects, via short-term plasticity, that depend on how calcium channels are regulated. Thus, DORs engage differential signaling cascades to regulate inhibition depending on the postsynaptic target compartment, with different effects on synaptic information transfer in somatic and dendritic domains.http://www.sciencedirect.com/science/article/pii/S2211124725000646CP: Neuroscience |
| spellingShingle | Ryan P.D. Alexander Kevin J. Bender Delta opioid receptors engage multiple signaling cascades to differentially modulate prefrontal GABA release with input and target specificity Cell Reports CP: Neuroscience |
| title | Delta opioid receptors engage multiple signaling cascades to differentially modulate prefrontal GABA release with input and target specificity |
| title_full | Delta opioid receptors engage multiple signaling cascades to differentially modulate prefrontal GABA release with input and target specificity |
| title_fullStr | Delta opioid receptors engage multiple signaling cascades to differentially modulate prefrontal GABA release with input and target specificity |
| title_full_unstemmed | Delta opioid receptors engage multiple signaling cascades to differentially modulate prefrontal GABA release with input and target specificity |
| title_short | Delta opioid receptors engage multiple signaling cascades to differentially modulate prefrontal GABA release with input and target specificity |
| title_sort | delta opioid receptors engage multiple signaling cascades to differentially modulate prefrontal gaba release with input and target specificity |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725000646 |
| work_keys_str_mv | AT ryanpdalexander deltaopioidreceptorsengagemultiplesignalingcascadestodifferentiallymodulateprefrontalgabareleasewithinputandtargetspecificity AT kevinjbender deltaopioidreceptorsengagemultiplesignalingcascadestodifferentiallymodulateprefrontalgabareleasewithinputandtargetspecificity |