Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
J Physiol. 2020 Dec;598(23):5523-5539. doi: 10.1113/JP280412. Epub 2020 Sep 18.
Fasting can increase motivation for food and can energize reward-seeking. Ventral tegmental area (VTA) dopamine neurons respond to motivationally relevant information and fasting can influence mesolimbic dopamine concentration. An acute overnight fast differentially alters food approach behaviours and excitatory synaptic transmission onto VTA dopamine neurons of male or female mice. While inhibitory synapses onto VTA dopamine neurons are not altered by fasting in male or female mice, male mice had strengthened excitatory synapses whereas female mice had increased endocannabinoid-mediated short-term plasticity at excitatory synapses. These results help us understand how fasting differentially influences excitatory synaptic transmission onto dopamine neurons and may inform different strategies for fasting-induced food seeking by male and female mice.
Dopamine neurons in the ventral tegmental area (VTA) are important for energizing goal-directed behaviour towards food and are sensitive to changes in metabolic states. Fasting increases the incentive motivation for food and the mobilization of energy stores and has sex-dependent effects. However, it is unknown how acute fasting alters excitatory or inhibitory synaptic transmission onto VTA dopamine neurons. An acute 16 h overnight fast induced increased food-seeking behaviour that was more predominant in male mice. Fasting increased miniature excitatory postsynaptic current frequency and amplitude in male, but not female, mice. This effect was not due to altered release probability as there was no change in the paired pulse ratio, nor was it due to an altered postsynaptic response as there was no change in the AMPA receptor/NMDA receptor ratio or response to glutamate uncaging. However, this effect was consistent with an increase in the number of release sites. In addition, depolarization-induced suppression of excitation, a measure of short-term endocannabinoid-mediated plasticity, was enhanced in female but not male fasted mice. There were no fasting-induced changes at inhibitory synapses onto dopamine neurons of male or female mice. Taken together, these results demonstrate that fasting influences excitatory synapses differentially in male and female mice, but preserves inhibitory synapses onto dopamine neurons, indicating that the mesolimbic circuits of male and female mice respond differently to acute energy deprivation.
禁食可以增加对食物的动机，并激发对奖励的寻求。腹侧被盖区（VTA）多巴胺神经元对与动机相关的信息作出反应，而禁食可以影响中脑边缘多巴胺浓度。急性 overnight fast（一夜禁食）会以不同的方式改变雄性或雌性小鼠的食物接近行为和 VTA 多巴胺神经元的兴奋性突触传递。虽然禁食不会改变雄性或雌性小鼠 VTA 多巴胺神经元的抑制性突触，但雄性小鼠的兴奋性突触增强，而雌性小鼠的兴奋性突触的内源性大麻素介导的短期可塑性增加。这些结果有助于我们了解禁食如何以不同的方式影响多巴胺神经元的兴奋性突触传递，并为禁食诱导的雄性和雌性小鼠对食物的寻求提供不同的策略。
腹侧被盖区（VTA）中的多巴胺神经元对于激发对食物的目标导向行为以及对代谢状态变化的敏感性都很重要。禁食会增加对食物的激励动机和能量储存的动员，并且具有性别依赖性的影响。然而，目前尚不清楚急性禁食如何改变 VTA 多巴胺神经元的兴奋性或抑制性突触传递。急性 overnight fast（一夜禁食）诱导了增加的食物寻求行为，这种行为在雄性小鼠中更为明显。禁食增加了雄性小鼠但不增加雌性小鼠的小型兴奋性突触后电流的频率和幅度。这种影响不是由于释放概率的改变，因为没有改变成对脉冲比，也不是由于突触后反应的改变，因为 AMPA 受体/NMDA 受体比值或对谷氨酸非光解的反应没有改变。然而，这种效应与释放位点数量的增加是一致的。此外，去极化诱导的兴奋抑制（depolarization-induced suppression of excitation，DSE），一种短时间内内源性大麻素介导的可塑性的测量方法，在禁食的雌性小鼠中增强，但在雄性小鼠中没有增强。禁食对雄性或雌性小鼠的多巴胺神经元上的抑制性突触没有引起变化。综上所述，这些结果表明，禁食在雄性和雌性小鼠中以不同的方式影响兴奋性突触，但保留了多巴胺神经元上的抑制性突触，这表明雄性和雌性小鼠的中脑边缘回路对急性能量剥夺的反应不同。
