Hernandez Alex, Burton Amanda C, O'Donnell Patricio, Schoenbaum Geoffrey, Roesch Matthew R
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Department of Psychology and Program in Neuroscience and Cognitive Science, University of Maryland, College Park, Maryland 20742.
J Neurosci. 2015 Apr 22;35(16):6394-400. doi: 10.1523/JNEUROSCI.5096-14.2015.
It has been proposed that schizophrenia results, in part, from the inappropriate or spurious attribution of salience to cues in the environment. We have recently reported neural correlates of salience in the basolateral amygdala (ABL) of rats during learning in an odor-guided discrimination task. Here we tested whether this dopamine-dependent salience signal is altered in rats with neonatal ventral hippocampal lesions (NVHLs), a rodent model of schizophrenia. We found that ABL signals related to violations in reward prediction were only mildly affected by NVHL; however, neurons in rats with NVHLs showed significantly stronger selectivity during odor sampling, particularly for the more salient large-reward cue. The elevated cue-evoked activity in NVHL rats was correlated with heightened orienting behavior and also with changes in firing to the shifts in reward, suggesting that it reflected abnormal signaling of the large reward-predicting cue's salience. These results are broadly consistent with the proposal that schizophrenics suffer from enhanced signaling of salience.
有人提出,精神分裂症部分是由于对环境中的线索赋予了不适当或虚假的显著性。我们最近报道了在气味引导的辨别任务学习过程中,大鼠基底外侧杏仁核(ABL)中显著性的神经相关性。在这里,我们测试了这种多巴胺依赖性显著性信号在新生腹侧海马损伤(NVHL)大鼠(一种精神分裂症啮齿动物模型)中是否发生改变。我们发现,与奖励预测违反相关的ABL信号仅受到NVHL的轻微影响;然而,患有NVHL的大鼠的神经元在气味采样期间表现出显著更强的选择性,特别是对于更显著的大奖励线索。NVHL大鼠中线索诱发的活动增强与定向行为增强相关,也与奖励变化时的放电变化相关,这表明它反映了大奖励预测线索显著性的异常信号。这些结果与精神分裂症患者存在显著性信号增强的观点大致一致。