Section on Neuroplasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, 20892.
Hippocampus. 2018 Jul;28(7):512-522. doi: 10.1002/hipo.22950. Epub 2018 May 4.
Decreased motivation to seek rewards is a key feature of mood disorders that correlates with severity and treatment outcome. This anhedonia, or apathy, likely reflects impairment in reward circuitry, but the specific neuronal populations controlling motivation are unclear. Granule neurons generated in the adult hippocampus have been implicated in mood disorders, but are not generally considered as part of reward circuits. We investigated a possible role of these new neurons in motivation to work for food and sucrose rewards in operant conditioning tasks using GFAP-TK pharmacogenetic ablation of adult neurogenesis in both rats and mice. Rats and mice lacking adult neurogenesis showed normal lever press responding during fixed ratio training, reward devaluation, and Pavlovian Instrumental Transfer, suggesting no impairment in learning. However, on an exponentially progressive ratio schedule, or when regular chow was freely available in the testing chamber, TK rats and mice showed less effort to gain sucrose tablets. When working for balanced food tablets, which rats and mice of both genotypes strongly preferred over sucrose, the genotype effects on behavior were lost. This decrease in effort under conditions of low reward suggests that loss of adult neurogenesis decreases motivation to seek reward in a manner that may model behavioral apathy.
寻求奖励的动机降低是心境障碍的一个关键特征，与严重程度和治疗效果相关。这种快感缺失或冷漠，可能反映了奖励回路的损伤，但控制动机的特定神经元群体尚不清楚。成年海马体中产生的颗粒神经元与心境障碍有关，但通常不被认为是奖励回路的一部分。我们使用 GFAP-TK 药理学基因消融成年神经发生，在大鼠和小鼠中研究了这些新神经元在操作条件反射任务中对食物和蔗糖奖励的工作动机的可能作用。缺乏成年神经发生的大鼠和小鼠在固定比率训练、奖励贬值和巴甫洛夫仪器转移期间表现出正常的杠杆按压反应，表明学习没有受损。然而，在指数递增比率方案中，或者当测试室中可以自由获得常规食物时，TK 大鼠和小鼠获得蔗糖片的努力较少。当为平衡的食物片工作时，两种基因型的大鼠和小鼠都强烈偏好食物片而不是蔗糖片，行为的基因型效应消失了。在低奖励条件下，这种努力的减少表明，成年神经发生的丧失以可能模拟行为冷漠的方式降低了寻求奖励的动机。
