Department of Pharmacology, University of Maryland School of Medicine, 670 W. Baltimore St. HSF III 9179, Baltimore, MD, 21201, USA.
Neuropsychopharmacology. 2019 May;44(6):1114-1122. doi: 10.1038/s41386-019-0341-8. Epub 2019 Feb 13.
The nucleus accumbens is a critical integration center for reward-related circuitry and is comprised primarily of medium spiny projection neurons. The dynamic balance of excitation and inhibition onto medium spiny neurons determines the output of this structure. While nucleus accumbens excitatory synaptic plasticity is well-characterized, inhibitory synaptic plasticity mechanisms and their potential relevance to shaping motivated behaviors is poorly understood. Here we report the discovery of long-term depression of inhibitory synaptic transmission in the mouse nucleus accumbens core. This long-term depression is postsynaptically expressed, tropomyosin kinase B (TrkB) receptor-mediated, and augmented in the presence of ethanol. Our findings support the emerging view that TrkB signaling regulates inhibitory synaptic plasticity and suggest this mechanism in the nucleus accumbens as a target for ethanol modulation of reward.
伏隔核是与奖励相关的回路的关键整合中心，主要由中型棘突投射神经元组成。中型棘突神经元上的兴奋和抑制的动态平衡决定了该结构的输出。虽然伏隔核兴奋性突触可塑性已经得到很好的描述，但抑制性突触可塑性机制及其对塑造动机行为的潜在相关性知之甚少。在这里，我们报告了在小鼠伏隔核核心中发现抑制性突触传递的长时程压抑。这种长时程压抑是突触后表达的，与原肌球蛋白激酶 B（TrkB）受体有关，并且在乙醇存在下增强。我们的发现支持了 TrkB 信号转导调节抑制性突触可塑性的新观点，并表明伏隔核中的这种机制是乙醇调节奖励的靶点。
