Neural Activity of the Frontal Cortex in Interval Timing

描述（由申请人提供）： 对时间的感知在秒到分钟的范围内，间隔计时，是行为的基础。 各种药物的急性和慢性给药导致时间知觉的改变，这种改变可能在这些药物的使用和滥用中起作用。了解间隔时间的心理和神经机制，以及药物使用所带来的变化，可能会提供重要的见解，以了解药物使用的过程范围。虽然以前的工作表明皮质-纹状体-丘脑回路在间隔计时中的作用，但这些大脑结构执行的具体计算仍然未知。间隔计时的模型已经提出，皮层活动作为时间信号的来源，由纹状体整合以估计时间。然而，这种皮层信号的特定模式是有争议的，并且可以通过振荡机制、放电率的线性或非线性增加/减少、时间特定的峰值功能或其他更复杂的放电模式来实现。本研究通过对大鼠进行间隔计时实验，采用细胞外记录技术研究额叶皮层在间隔计时中的作用。具体而言，将训练大鼠在音调信号开始后5秒和30秒的2个不同时间点进行鼻戳。他们还将接受训练，在一个不可预测的时间，以回应不同的音调鼻子接受食物。训练后，将电极长期植入背内侧额叶皮质和背侧前纹状体。 在试验中，将单个神经元的活动作为时间的函数进行评估，以确定总体放电模式（斜坡、峰值、振荡）。还将在不同时间的等效行为（即，5秒对30秒）或没有时间特异性预期（随机比率计划），以评估额叶皮层代表时间、一般预期或运动准备的程度。将研究甲基苯丙胺给药后放电频率/模式的变化。

DESCRIPTION (provided by applicant): The perception of time in the seconds to minutes range, interval timing, is fundamental to behavior. Alterations in temporal perception result from the acute and chronic administration of a variety of drugs, and such alterations may play a part in the use and abuse of these drugs. Understanding the psychological and neural mechanisms of interval timing, as well as the changes brought on by drug use, may provide important insights into the range of processes that underlie drug use. While previous work has suggested a role for cortico-striatal-thalamic loops in interval timing, the specific computations performed by these brain structures remain unknown. Models of interval timing have proposed that cortical activity serves as the source of a temporal signal that is integrated by the striatum to estimate time. However, the specific pattern of this cortical signal is debated, and may be subserved by oscillatory mechanisms, linear or non-linear increases/decreases in firing rates, temporally specific peak functions, or other, more complex, firing patterns. The present proposal will investigate the role of frontal cortex in interval timing, through the use of ensemble extracellular recording techniques in rats performing an interval timing task. Specifically, rats will be trained to nosepoke at 2 distinct times, 5 and 30 seconds after onset of a tone signal. They will also be trained to nosepoke to receive food at an unpredictable time in response to a different tone. Following training, electrodes will be chronically implanted into dorsal medial frontal cortex and dorsal anterior striatum. Activity from single neurons will be evaluated as a function of time in the trial to determine the overall firing pattern (ramp, peak, oscillation). Firing rates will also be compared across different times of equivalent behavior (i.e., 5 sec vs. 30 sec) or without a temporally-specific expectation (random ratio schedule) to evaluate whether the degree to which frontal cortex represents time, general expectancy, or motor preparation. Changes in firing rates/patterns following methamphetamine administration will be investigated.