Harvard Medical School, McLean Hospital, Belmont, MA, 02478, USA.
Department of Child and Adolescent Psychiatry, Columbia University, New York, NY, 10032, USA.
Neuropsychopharmacology. 2023 Mar;48(4):700-709. doi: 10.1038/s41386-023-01532-4. Epub 2023 Jan 16.
Blunted reward learning and reward-related activation within the corticostriatal-midbrain circuitry have been implicated in the pathophysiology of anhedonia and depression. Unfortunately, the search for more efficacious interventions for anhedonic behaviors has been hampered by the use of vastly different preclinical and clinical assays. In a first step in addressing this gap, in the current study, we used event-related potentials and spectral analyses in conjunction with a touchscreen version of the rodent Probabilistic Reward Task (PRT) to identify the electrophysiological signatures of reward learning in rats. We trained 11 rats (5 females and 6 males) on the rodent touchscreen-based PRT and subsequently implanted them with deep electrodes in the anterior cingulate cortex (ACC) and nucleus accumbens (NAc) for local field potentials recordings during the PRT. Behaviorally, the expected responsivity-to-reward profile was observed. At the electrophysiological level, we identified a negative amplitude deflection 250-500 ms after feedback in the ACC and NAc electrodes, as well as power increase in feedback-locked delta (1-5 Hz) and alpha/beta (9-17 Hz) bands in both electrodes for rewarded trials. Using a reverse-translational approach, we identified electrophysiological signatures of reward learning in rats similar to those described in humans. These findings and approaches might provide a useful translational platform to efficiently evaluate novel therapeutics targeting anhedonia.
奖赏学习能力下降以及皮质纹状体-中脑回路中的奖赏相关激活与快感缺失和抑郁的病理生理学有关。不幸的是,由于使用了截然不同的临床前和临床检测方法,寻找更有效的治疗快感缺失行为的方法受到了阻碍。在解决这一差距的第一步中,在当前的研究中,我们使用事件相关电位和频谱分析以及啮齿动物概率奖赏任务(PRT)的触摸屏版本,来确定大鼠奖赏学习的电生理特征。我们在基于啮齿动物的触摸屏 PRT 上对 11 只大鼠(5 只雌性和 6 只雄性)进行了训练,随后在它们的前扣带回皮层(ACC)和伏隔核(NAc)中植入深部电极,以便在 PRT 期间进行局部场电位记录。行为上,观察到了预期的反应性-奖赏模式。在电生理水平上,我们在 ACC 和 NAc 电极中观察到反馈后 250-500ms 时的负幅度偏转,以及反馈锁定的 delta(1-5Hz)和 alpha/beta(9-17Hz)波段在两个电极中都有功率增加,用于奖励试验。使用一种逆向转化方法,我们在大鼠中鉴定出了与人类描述相似的奖赏学习的电生理特征。这些发现和方法可能为有效地评估针对快感缺失的新型治疗方法提供一个有用的转化平台。