Rodent Medial Frontal Control of Temporal Processing in the Dorsomedial Striatum

Abstract

Although frontostriatal circuits are critical for the temporal control of action, how time is encoded in frontostriatal circuits is unknown. We recorded from frontal and striatal neurons while rats engaged in interval timing, an elementary cognitive function that engages both areas. We report four main results. First, "ramping" activity, a monotonic change in neuronal firing rate across time, is observed throughout frontostriatal ensembles. Second, frontostriatal activity scales across multiple intervals. Third, striatal ramping neurons are correlated with activity of the medial frontal cortex. Finally, interval timing and striatal ramping activity are disrupted when the medial frontal cortex is inactivated. Our results support the view that striatal neurons integrate medial frontal activity and are consistent with drift-diffusion models of interval timing. This principle elucidates temporal processing in frontostriatal circuits and provides insight into how the medial frontal cortex exerts top-down control of cognitive processing in the striatum.SIGNIFICANCE STATEMENT The ability to guide actions in time is essential to mammalian behavior from rodents to humans. The prefrontal cortex and striatum are critically involved in temporal processing and share extensive neuronal connections, yet it remains unclear how these structures represent time. We studied these two brain areas in rodents performing interval-timing tasks and found that time-dependent "ramping" activity, a monotonic increase or decrease in neuronal activity, was a key temporal signal. Furthermore, we found that striatal ramping activity was correlated with and dependent upon medial frontal activity. These results provide insight into information-processing principles in frontostriatal circuits.

Keywords: Parkinson's disease; dorsomedial striatum; medial frontal cortex; medium spiny neurons; prefrontal cortex; timing.