Department of Psychology, University of Michigan, Ann Arbor, Michigan 48109, USA.
J Neurosci. 2012 Aug 29;32(35):12115-28. doi: 10.1523/JNEUROSCI.2271-12.2012.
Although the impairments in cognitive performance that result from shifting or disrupting daily rhythms have been demonstrated, the neuronal mechanisms that optimize fixed-time daily performance are poorly understood. We previously demonstrated that daily practice of a sustained attention task (SAT) evokes a diurnal activity pattern in rats. Here, we report that SAT practice at a fixed time produced practice time-stamped increases in prefrontal cholinergic neurotransmission that persisted after SAT practice was terminated and in a different environment. SAT time-stamped cholinergic activation occurred regardless of whether the SAT was practiced during the light or dark phase or in constant-light conditions. In contrast, prior daily practice of an operant schedule of reinforcement, albeit generating more rewards and lever presses per session than the SAT, neither activated the cholinergic system nor affected the animals' nocturnal activity pattern. Likewise, food-restricted animals exhibited strong food anticipatory activity (FAA) and attenuated activity during the dark phase but FAA was not associated with increases in prefrontal cholinergic activity. Removal of cholinergic neurons impaired SAT performance and facilitated the reemergence of nocturnality. Shifting SAT practice away from a fixed time resulted in significantly lower performance. In conclusion, these experiments demonstrated that fixed-time, daily practice of a task assessing attention generates a precisely practice time-stamped activation of the cortical cholinergic input system. Time-stamped cholinergic activation benefits fixed-time performance and, if practiced during the light phase, contributes to a diurnal activity pattern.
虽然已经证明，日常节律的改变或扰乱会导致认知表现受损，但优化固定时间日常表现的神经元机制仍知之甚少。我们之前曾证明，每天进行持续注意力任务（SAT）练习会在大鼠中引起昼夜活动模式。在这里，我们报告称，在固定时间进行 SAT 练习会产生与练习时间标记相关的前额叶胆碱能神经传递的增加，这种增加在 SAT 练习终止后并在不同环境中仍然存在。无论 SAT 是在光照或黑暗阶段进行，还是在持续光照条件下进行，SAT 都会产生时间标记的胆碱能激活。相比之下，尽管先前每日进行操作性强化计划的练习产生的奖励和杠杆按压次数比 SAT 多，但既没有激活胆碱能系统，也没有影响动物的夜间活动模式。同样，限制食物的动物表现出强烈的食物预期活动（FAA）和黑暗阶段活动减少，但 FAA 与前额叶胆碱能活动的增加无关。去除胆碱能神经元会损害 SAT 表现并促进夜间活动的重新出现。将 SAT 练习从固定时间转移会导致表现明显下降。总之，这些实验表明，固定时间、每日进行注意力评估任务的练习会产生与练习时间标记精确相关的皮质胆碱能输入系统的激活。时间标记的胆碱能激活有利于固定时间的表现，如果在光照阶段进行练习，有助于昼夜活动模式的形成。
