Centre National de la Recherche Scientifique, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, F-67000 Strasbourg, France; Unitat Predepartamental de Medicina, Universitat Jaume I, Castelló de la Plana, Spain.
Centre National de la Recherche Scientifique, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, F-67000 Strasbourg, France.
Behav Brain Res. 2022 May 3;425:113826. doi: 10.1016/j.bbr.2022.113826. Epub 2022 Mar 2.
The tail of the ventral tegmental area (tVTA) or rostromedial tegmental nucleus (RMTg) receives lateral habenula inputs and projects heavily to midbrain dopamine neurons. Midbrain dopamine and lateral habenula neurons participate in learning processes predicting the outcomes of actions, placing the tVTA in a critical location into prediction error pathways. tVTA GABA neurons show electrophysiological inhibition or activation after reward and aversive stimuli, respectively, and their predictive cues. tVTA molecular recruitment, however, is not elicited by all aversive stimuli. Indeed, precipitated opioid withdrawal, repeated footshocks or food restriction raise tVTA Fos expression, whereas various other unpleasant, stressful or painful stimuli does not elicit that molecular response. However, the basis of that difference remains unknown. In the present study, we tried to disentangle whether the tVTA c-Fos induction observed after food restriction was due to the aversive state of food restriction or to procedure-related reward prediction error. To this end, male Sprague-Dawley rats were food-restricted for 7-8 days. During this period, animals were handled and weighed every day before feeding. On the test day, rats underwent several behavioral procedures to explore the impact of food restriction and food-predictive cue exposure on tVTA c-Fos expression. We showed that food restriction per se was not able to recruit c-Fos in the tVTA. On the contrary, the food-predicting cues induced c-Fos locally in the absence of feeding, whereas the food-predicting cues followed by feeding evoked lower c-Fos expression. Overall, our results support the proposed involvement of the tVTA in reward prediction error.
腹侧被盖区（VTA）尾部或中脑导水管周围灰质腹侧部（RMTg）接收外侧缰核的输入，并大量投射到中脑多巴胺神经元。中脑多巴胺和外侧缰核神经元参与预测行为结果的学习过程，使 VTA 处于预测误差途径的关键位置。VTA GABA 神经元在奖励和厌恶刺激后分别表现出电生理抑制或激活，以及它们的预测线索。然而，VTA 的分子募集并不被所有厌恶刺激引发。事实上，阿片类药物戒断、重复电击或食物限制会引起 VTA 的 Fos 表达升高，而其他各种不愉快、压力大或疼痛的刺激则不会引起这种分子反应。然而，这种差异的基础仍不清楚。在本研究中，我们试图厘清在食物限制后观察到的 VTA c-Fos 诱导是否是由于食物限制的厌恶状态还是由于与程序相关的奖励预测错误。为此，雄性 Sprague-Dawley 大鼠进行了 7-8 天的食物限制。在此期间，动物在喂食前每天都会被处理和称重。在测试日，大鼠进行了多项行为程序，以探讨食物限制和食物预测线索暴露对 VTA c-Fos 表达的影响。我们发现，食物限制本身并不能招募 VTA 中的 c-Fos。相反，在没有进食的情况下，食物预测线索会诱导 c-Fos 的局部表达，而在进食后，食物预测线索则会引起较低的 c-Fos 表达。总体而言，我们的结果支持 VTA 参与奖励预测错误的假说。
