Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Nature. 2018 Aug;560(7720):589-594. doi: 10.1038/s41586-018-0416-4. Epub 2018 Aug 8.
Dysfunction in prosocial interactions is a core symptom of autism spectrum disorder. However, the neural mechanisms that underlie sociability are poorly understood, limiting the rational development of therapies to treat social deficits. Here we show in mice that bidirectional modulation of the release of serotonin (5-HT) from dorsal raphe neurons in the nucleus accumbens bidirectionally modifies sociability. In a mouse model of a common genetic cause of autism spectrum disorder-a copy number variation on chromosome 16p11.2-genetic deletion of the syntenic region from 5-HT neurons induces deficits in social behaviour and decreases dorsal raphe 5-HT neuronal activity. These sociability deficits can be rescued by optogenetic activation of dorsal raphe 5-HT neurons, an effect requiring and mimicked by activation of 5-HT1b receptors in the nucleus accumbens. These results demonstrate an unexpected role for 5-HT action in the nucleus accumbens in social behaviours, and suggest that targeting this mechanism may prove therapeutically beneficial.
社交互动功能障碍是自闭症谱系障碍的核心症状。然而，社交能力的神经机制仍不清楚，这限制了针对社交缺陷的治疗方法的合理发展。在这里，我们在小鼠中表明，中缝背核神经元在伏隔核中释放的 5-羟色胺（5-HT）的双向调节可双向调节社交能力。在自闭症谱系障碍的常见遗传原因的小鼠模型中——16p11.2 染色体上的拷贝数变异——5-HT 神经元中的同基因区域的基因缺失会导致社交行为缺陷，并降低中缝背核 5-HT 神经元活性。这种社交缺陷可以通过光遗传学激活中缝背核 5-HT 神经元来挽救，这种效应需要并通过伏隔核中的 5-HT1b 受体的激活来模拟。这些结果表明 5-HT 在伏隔核中的作用在社交行为中具有意想不到的作用，并表明靶向这种机制可能具有治疗益处。
