Abstract:
The subthalamic nucleus (STN) is traditionally thought to restrict movement. Lesion or prolonged STN inhibition increases movement vigor and propensity, while optogenetic excitation has opposing effects. However, STN neurons often exhibit movement-related increases in firing. To address this paradox, STN activity was recorded and manipulated in head-fixed mice at rest and during self-initiated and self-paced treadmill locomotion. We found that (1) most STN neurons (type 1) exhibit locomotion-dependent increases in activity, with half firing preferentially during the propulsive phase of the contralateral locomotor cycle; (2) a minority of STN neurons exhibit dips in activity or are uncorrelated with movement; (3) brief optogenetic inhibition of the lateral STN (where type 1 neurons are concentrated) slows and prematurely terminates locomotion; and (4) in Q175 Huntington\'s disease mice, abnormally brief, low-velocity locomotion is associated with type 1 hypoactivity. Together, these data argue that movement-related increases in STN activity contribute to optimal locomotor performance.
摘要:
传统上认为丘脑底核(STN)限制运动。损伤或延长STN抑制增加运动活力和倾向,而光遗传学激发具有相反的作用。然而,STN神经元通常表现出与运动相关的放电增加。为了解决这个悖论,在休息时以及在自我启动和自我步调的跑步机运动期间,记录并操纵头部固定的小鼠的STN活性。我们发现(1)大多数STN神经元(1型)表现出运动依赖性的活动增加,在对侧运动周期的推进阶段优先进行半放电;(2)少数STN神经元表现出活动下降或与运动无关;(3)对外侧STN(1型神经元集中)的短暂光遗传学抑制减慢并过早终止运动;(4)在Q175亨廷顿病小鼠中,异常简短,低速运动与1型活动不足有关。一起,这些数据表明,与运动相关的STN活动增加有助于最佳的运动性能。