Alexander Ryan P D, Bender Kevin J
Weill 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.
Cell Rep. 2025 Feb 25;44(2):115293. doi: 10.1016/j.celrep.2025.115293. Epub 2025 Feb 8.
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.
阿片类药物调节大脑中与动机和奖赏相关的神经回路。在阿片受体类型中，δ阿片受体（DORs）似乎在调节与奖赏相关的神经回路活动中具有独特作用，且无滥用倾向。在新皮层中，DORs主要表达于中间神经元，包括分别表达小白蛋白和生长抑素的中间神经元，它们分别抑制兴奋性锥体细胞的胞体和树突部分。但DORs如何调节这些关键中间神经元类别的传递尚不清楚。我们发现，DORs利用不同的G蛋白信号通路调节来自这些中间神经元类别的抑制作用，这些信号通路都汇聚于突触前钙通道，但调节钙通道功能的不同方面。这通过短期可塑性施加了不同的时间滤波效应，这取决于钙通道的调节方式。因此，DORs根据突触后靶区参与不同的信号级联反应来调节抑制作用，对胞体和树突区域的突触信息传递有不同影响。
