Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Departments of Neuroscience and Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.
Science. 2021 Apr 2;372(6537). doi: 10.1126/science.abf4740.
Hallucinations, a central symptom of psychotic disorders, are attributed to excessive dopamine in the brain. However, the neural circuit mechanisms by which dopamine produces hallucinations remain elusive, largely because hallucinations have been challenging to study in model organisms. We developed a task to quantify hallucination-like perception in mice. Hallucination-like percepts, defined as high-confidence false detections, increased after hallucination-related manipulations in mice and correlated with self-reported hallucinations in humans. Hallucination-like percepts were preceded by elevated striatal dopamine levels, could be induced by optogenetic stimulation of mesostriatal dopamine neurons, and could be reversed by the antipsychotic drug haloperidol. These findings reveal a causal role for dopamine-dependent striatal circuits in hallucination-like perception and open new avenues to develop circuit-based treatments for psychotic disorders.
幻觉是精神障碍的核心症状之一,被认为与大脑中多巴胺的过量有关。然而,多巴胺产生幻觉的神经回路机制仍难以捉摸,主要是因为在模型生物中研究幻觉具有挑战性。我们开发了一种量化小鼠幻觉样感知的任务。幻觉样知觉被定义为高置信度的假阳性检测,在小鼠的幻觉相关操作后增加,并且与人类自我报告的幻觉相关。在纹状体多巴胺水平升高之前出现幻觉样知觉,可以通过中脑多巴胺神经元的光遗传学刺激诱导,并且可以被抗精神病药物氟哌啶醇逆转。这些发现揭示了多巴胺依赖的纹状体回路在幻觉样感知中的因果作用,并为开发针对精神障碍的基于回路的治疗方法开辟了新途径。