National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20814 and.
National Institute on Drug Abuse, Baltimore, Maryland 21224.
J Neurosci. 2018 Apr 4;38(14):3547-3558. doi: 10.1523/JNEUROSCI.2693-17.2018. Epub 2018 Mar 9.
The striatum controls food-related actions and consumption and is linked to feeding disorders, including obesity and anorexia nervosa. Two populations of neurons project from the striatum: direct pathway medium spiny neurons and indirect pathway medium spiny neurons. The selective contribution of direct pathway medium spiny neurons and indirect pathway medium spiny neurons to food-related actions and consumption remains unknown. Here, we used electrophysiology and fiber photometry in mice (of both sexes) to record both spiking activity and pathway-specific calcium activity of dorsal striatal neurons during approach to and consumption of food pellets. While electrophysiology revealed complex task-related dynamics across neurons, population calcium was enhanced during approach and inhibited during consumption in both pathways. We also observed ramping changes in activity that preceded both pellet-directed actions and spontaneous movements. These signals were heterogeneous in the spiking units, with neurons exhibiting either increasing or decreasing ramps. In contrast, the population calcium signals were homogeneous, with both pathways having increasing ramps of activity for several seconds before actions were initiated. An analysis comparing population firing rates to population calcium signals also revealed stronger ramping dynamics in the calcium signals than in the spiking data. In a second experiment, we trained the mice to perform an action sequence to evaluate when the ramping signals terminated. We found that the ramping signals terminated at the beginning of the action sequence, suggesting they may reflect upcoming actions and not preconsumption activity. Plasticity of such mechanisms may underlie disorders that alter action selection, such as drug addiction or obesity. Alterations in striatal function have been linked to pathological consumption in disorders, such as obesity and drug addiction. We recorded spiking and population calcium activity from the dorsal striatum during feeding and an operant task that resulted in mice obtaining food pellets. Dorsal striatal neurons exhibited long ramps in activity that preceded actions by several seconds, and may reflect upcoming actions. Understanding how the striatum controls the preparation and generation of actions may lead to improved therapies for disorders, such as drug addiction or obesity.
纹状体控制与食物相关的行为和摄食,与摄食障碍有关,包括肥胖和神经性厌食症。两种神经元群从纹状体投射:直接通路中型棘突神经元和间接通路中型棘突神经元。直接通路中型棘突神经元和间接通路中型棘突神经元对与食物相关的行为和摄食的选择性贡献尚不清楚。在这里,我们使用电生理学和纤维光度法在雄性和雌性小鼠中记录背侧纹状体神经元在接近和消耗食物颗粒时的放电活动和通路特异性钙活性。虽然电生理学揭示了神经元之间复杂的任务相关动力学,但在两条通路上,群体钙在接近时增强,在消耗时抑制。我们还观察到在颗粒定向动作和自发运动之前,活动呈斜坡变化。这些信号在尖峰单元中是异构的,神经元表现出增加或减少的斜坡。相比之下,群体钙信号是同质的,在开始动作之前,两条通路的活动都有几秒钟的斜坡增加。比较群体放电率与群体钙信号的分析也显示,钙信号中的斜坡动力学比尖峰数据更强。在第二个实验中,我们训练老鼠执行一个动作序列,以评估斜坡信号何时终止。我们发现,斜坡信号在动作序列开始时终止,这表明它们可能反映即将到来的动作,而不是摄食前的活动。改变这些机制的可塑性可能是改变动作选择的疾病的基础,例如药物成瘾或肥胖。纹状体功能的改变与肥胖和药物成瘾等疾病的病理性摄食有关。我们在进食和操作性任务期间记录了背侧纹状体的尖峰和群体钙活动,该任务导致老鼠获得食物颗粒。背侧纹状体神经元在动作前几秒钟表现出长斜坡的活动,可能反映即将到来的动作。了解纹状体如何控制动作的准备和产生可能会为药物成瘾或肥胖等疾病的治疗带来改善。