Neural Activity of the Frontal Cortex in Interval Timing

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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.