Herring Ethan W, Lear Kira B, Zeng Sandford, McLaughlin Elin F B, Syamala Tulasi, Patel Eesha D, Duffer Kyle, Morrison Sara E
Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260.
Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260
J Neurosci. 2025 Jun 25;45(26):e0061252025. doi: 10.1523/JNEUROSCI.0061-25.2025.
When a cue is located away from its associated reward, some animals will learn to approach the site of reward (goal-tracking behavior) while others will approach the cue (sign-tracking behavior). The acquisition of sign tracking, but not goal tracking, is dependent on dopamine in the nucleus accumbens (NAc), and we have previously demonstrated that reward-evoked activity in the NAc core may reflect different patterns of dopamine release in sign tracker versus goal tracker individuals. However, a causal relationship among dopamine release, NAc activity, and sign tracking has not been established. Using male and female TH::Cre rats, we expressed inhibitory or excitatory opsins in dopamine neurons of the ventral tegmental area (VTA) and examined the impact of optical manipulation of dopamine neurons on behavior and concurrent NAc neuronal activity. We found that inhibition of VTA dopamine neurons at the time of reward suppressed the acquisition of sign-tracking, but not goal-tracking, behavior. On the other hand, stimulation of dopamine neurons did not alter the acquisition of sign tracking; however, cessation of stimulation impeded further acquisition of sign tracking. Finally, both inhibition and stimulation of VTA dopamine neurons rapidly modulated activity in a subset of NAc neurons and led to changes in cue- and reward-related activity across sessions. Overall, these findings support the ideas that sign tracking and goal tracking are the products of two different learning processes-one dopamine-dependent and one not-and that the impact of VTA dopamine on sign tracking may be mediated by activity in the NAc core.
当一个线索与它相关的奖励位置分开时,一些动物会学会接近奖励的位置(目标追踪行为),而另一些动物会接近线索(信号追踪行为)。信号追踪而非目标追踪的习得依赖于伏隔核(NAc)中的多巴胺,并且我们之前已经证明,NAc核心中奖励诱发的活动可能反映了信号追踪者与目标追踪者个体中多巴胺释放的不同模式。然而,多巴胺释放、NAc活动和信号追踪之间的因果关系尚未确立。我们使用雄性和雌性TH::Cre大鼠,在腹侧被盖区(VTA)的多巴胺神经元中表达抑制性或兴奋性视蛋白,并研究对多巴胺神经元进行光操纵对行为和同时发生的NAc神经元活动的影响。我们发现,在奖励时抑制VTA多巴胺神经元会抑制信号追踪行为的习得,但不会抑制目标追踪行为。另一方面,刺激多巴胺神经元不会改变信号追踪的习得;然而,停止刺激会阻碍信号追踪的进一步习得。最后,对VTA多巴胺神经元的抑制和刺激都会迅速调节NAc神经元子集中的活动,并导致各实验环节中与线索和奖励相关的活动发生变化。总体而言,这些发现支持以下观点:信号追踪和目标追踪是两种不同学习过程的产物——一种依赖多巴胺,另一种不依赖多巴胺——并且VTA多巴胺对信号追踪的影响可能由NAc核心中的活动介导。
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