To study the effect of cholinergic inhibition on the medial prefrontal cortex (mPFC) during an interval timing task in freely behaving animals.

Cholinergic deficit is a major feature in patients with Alzheimer’s disease, Parkinson’s disease dementia and dementia with Lewy bodies. Parkinson’s and Alzheimer’s patients can have impairments in interval timing, or the ability to control movements in time. Timing is preserved across mammalian species, and timing tasks require subjects to estimate an interval of several seconds. These tasks require attention to time and working memory for temporal rules. Mice receiving scopolamine, a cholinergic inhibitor, perform poorly during timing tasks. Interval timing involves medial prefrontal cortical areas that receive prominent cholinergic input; however, the effect of cholinergic inhibition on the mPFC network activities during interval timing has not been studied.     

Wild-type mice were trained on a 12s interval timing task before 16-channel microelectrode arrays were implanted into the mPFC (AP +1.8, ML -0.5, DV -1.8). Neuronal ensemble recordings were performed during the task 30 min after intraperitoneal scopolamine (1mg/kg) or vehicle injections.

Scopolamine caused interval-timing deficits in wild type mice, with associated enhancement in the mPFC low frequency cortical rhythms as well as decreased proportion of “ramping” neurons. “Ramping” neurons are associated with temporal control and change firing rates during the 12s interval timing task.

Cholinergic inhibition through scopolamine enhances low frequency mPFC rhythms and impairs temporal processing in wild type mice. These data may have relevance for our understanding of cholinergic function in human diseases such as Parkinson’s disease and Alzheimer’s disease.