Mechanisms of sound sequence discrimination learning motivated by reward in the rat

我们之前报道过声音序列辨别学习需要向大鼠听觉皮层（AC）输入胆碱能。在那项研究中，奖励被用来激励大鼠的歧视行为。因此，多巴胺能输入介导奖励信号可能在学习中起重要作用。我们在本研究中检验了这种可能性。老鼠被训练来区分两种声音成分的序列，对其中一种声音序列做出反应的舔舐行为会得到水的奖励。为了确定负责学习的多巴胺能输入，局部注射6-羟基多巴胺（6-OHDA）损伤AC的多巴胺能传入。注射减弱了声音序列识别学习，但对序列刺激中声音成分的识别没有影响。伏隔核局部注射6-羟多巴胺可减弱辨音学习。然而，不仅声音序列的辨别学习受到损害，声音成分的辨别学习也受到损害。D1受体拮抗剂SCH23390 （0.2mg/kg, i.p）对声音序列识别学习无影响，但对陌生刺激的舔舐行为有减弱作用。D2家族拮抗剂氟哌啶醇（0.5 mg/kg, i.p）对声音序列识别学习有减弱作用，而对两种不同声音成分的识别和舔舐无明显抑制作用。这些结果表明D2家族受体被多巴胺能输入AC激活是声音序列识别学习所必需的。

We have previously reported that sound sequence discrimination learning requires cholinergic inputs to the auditory cortex (AC) in rats. In that study, reward was used for motivating discrimination behavior in rats. Therefore, dopaminergic inputs mediating reward signals may have an important role in the learning. We tested the possibility in the present study. Rats were trained to discriminate sequences of two sound components, and licking behavior in response to one of the two sequences was rewarded with water. To identify the dopaminergic inputs responsible for the learning, dopaminergic afferents to the AC were lesioned with local injection of 6-hydroxydopamine (6-OHDA). The injection attenuated sound sequence discrimination learning, while it had no effect on discrimination between the sound components of the sequence stimuli. Local injection of 6-OHDA into the nucleus accumbens attenuated sound discrimination learning. However, not only discrimination learning of sound sequence but also that of the sound components were impaired. SCH23390 (0.2mg/kg, i.p.), a D1 receptor antagonist, had no effect on sound sequence discrimination learning, while it attenuated the licking behavior to unfamiliar stimuli. Haloperidol (0.5 mg/kg, i.p.), a D2 family antagonist, attenuated sound sequence discrimination learning, while it had no clear suppressive effect on discrimination of two different sound components and licking. These results suggest that D2 family receptors activated by dopaminergic inputs to the AC are required for sound sequence discrimination learning.