Department of Psychology, Vanderbilt University, Nashville, TN, USA.
Vanderbilt Brain Institute, Nashville, TN, USA.
Nat Commun. 2024 Nov 15;15(1):9905. doi: 10.1038/s41467-024-54395-8.
The noradrenergic system is believed to support behavioral flexibility. A possible source mediating improved flexibility are α2A adrenoceptors (α2AR) in prefrontal cortex (PFC) or the anterior cingulate cortex (ACC). We tested this hypothesis by stimulating α2ARs using Guanfacine during attentional set shifting in male nonhuman primates. We found that α2AR stimulation improved learning from errors and updating attention sets. Neural recordings in the ACC, dorsolateral PFC, and the striatum showed that α2AR stimulation selectively enhanced neural signaling of prediction errors in neurons of the ACC and the striatum, but not in dlPFC. This modulation was accompanied by enhanced encoding of attended target features and particularly apparent in putative fast-spiking interneurons, pointing to an interneuron mediated mechanism of α2AR action. These results reveal that α2A receptors are part of the causal chain of flexibly updating attention sets through an enhancement of outcomes and prediction error signaling in ACC and striatum.
去甲肾上腺素能系统被认为支持行为灵活性。调节改善灵活性的一个可能的介质是前额叶皮层（PFC）或前扣带皮层（ACC）中的α2A 肾上腺素能受体（α2AR）。我们通过在雄性非人类灵长类动物的注意力设置转移期间使用胍法辛刺激α2AR 来测试这一假设。我们发现α2AR 刺激可改善错误学习和更新注意力设置。在 ACC、背外侧 PFC 和纹状体中的神经记录显示，α2AR 刺激选择性增强了 ACC 和纹状体神经元中预测误差的神经信号，而不是在 dlPFC 中。这种调制伴随着对注意目标特征的增强编码，特别是在假定的快速发射中间神经元中更为明显，表明α2AR 作用的中间神经元介导机制。这些结果表明，α2A 受体是通过增强 ACC 和纹状体中的结果和预测错误信号来灵活更新注意力设置的因果链的一部分。
