Dopamine guides behavior and learning through pleasure, according to classic understanding. Dopaminergic neurons are traditionally thought to signal positive or negative prediction errors (PEs) when reward expectations are, respectively, exceeded or not matched. These signed PEs are quite different from the unsigned PEs, which report surprise during sensory processing. But mounting theoretical accounts from the predictive processing framework postulate that dopamine, as a neuromodulator, could potentially regulate the postsynaptic gain of sensory neurons, thereby scaling unsigned PEs according to their expected precision or confidence. Despite ample modeling work, the physiological effects of dopamine on the processing of surprising sensory information are yet to be addressed experimentally. In this study, we tested how dopamine modulates midbrain processing of unexpected tones. We recorded extracellular responses from the rat inferior colliculus to oddball and cascade sequences, before, during, and after the microiontophoretic application of dopamine or eticlopride (a D₂-like receptor antagonist). Results demonstrate that dopamine reduces the net neuronal responsiveness exclusively to unexpected sensory input without significantly altering the processing of expected input. We conclude that dopaminergic projections from the thalamic subparafascicular nucleus to the inferior colliculus could encode the expected precision of unsigned PEs, attenuating via D₂-like receptors the postsynaptic gain of sensory inputs forwarded by the auditory midbrain neurons. This direct dopaminergic modulation of sensory PE signaling has profound implications for both the predictive coding framework and the understanding of dopamine function.

根据经典的理解，多巴胺通过愉悦引导行为和学习。传统上认为，多巴胺能神经元分别在奖励期望被超过或不匹配时发出正或负的预测错误（PE）。这些签名的PE与未签名的PE完全不同，后者在感觉处理过程中会报告意外。但是从预测性处理框架中获得的理论解释认为，多巴胺作为一种神经调节剂，可以潜在地调节感觉神经元的突触后增益，从而根据其预期的精确度或置信度来缩放未签名的PE。尽管进行了大量的建模工作，但多巴胺在处理令人惊讶的感觉信息方面的生理效应仍需通过实验解决。在这个研究中，我们测试了多巴胺如何调节意想不到的音调的中脑处理。我们记录了大鼠下丘脑对奇异球和级联序列的细胞外反应，在多巴胺或依托必利的微离子电渗疗法应用之前，之中和之后（D₂样受体拮抗剂）。结果表明，多巴胺仅降低了对意外感觉输入的净神经元反应，而没有显着改变预期输入的处理。我们得出的结论是，从丘脑束下丘脑核到下丘的多巴胺能投射可以编码未签名PE的预期精度，并通过D ₂样受体减弱由听觉中脑神经元转发的感觉输入的突触后增益。感觉性PE信号的这种直接多巴胺能调制对预测编码框架和对多巴胺功能的理解都具有深远的意义。