Khandelwal, V. | bioRxiv Science

bioRxiv2025

Timing, movement, and reward contributions to prefrontal and striatal ramping activity

Across species, prefrontal and striatal neurons exhibit time-dependent ramping activity, defined as a consistent monotonic change in firing rate across temporal intervals. However, it is unclear if ramping activity is related to the cognitive process of estimating time, or to other behavioral factors such as anticipating reward or regulating movements. Here, we harnessed two novel approaches to determine how these factors contribute to prefrontal and striatal ramping activity in mice performing an interval timing task. First, to determine how movement contributes to ramping activity, we tracked movement velocity using DeepLabCut as well as task-specific movements while recording prefrontal or striatal ensembles during interval timing. We found that time was more accurately decoded by ramping neurons than movement-modulated neurons, with the exception of prefrontal velocity-modulated neurons. Second, to disambiguate temporal signals from anticipatory reward signals we compared activity patterns in neurons that were recorded during interval timing to the same neurons recorded during a Pavlovian conditioning task. We found more ramping activity and more accurate temporal decoding by neuronal ensembles during interval timing compared to Pavlovian conditioning. Together, these data quantify contributions of time estimation, movement, and reward anticipation in prefrontal and striatal ensembles, and they suggest that ramping is a cognitive signal that estimates time. Our results provide insight into how prefrontal and striatal ensembles multiplex information to effect temporal control of action.

neuroscience↗

bioRxiv2022

Mice expressing P301S mutant human tau have deficits in interval timing

Interval timing is a key executive process that involves estimating the duration of an interval over several seconds or minutes. Patients with Alzheimers disease (AD) have deficits in interval timing. Since temporal control of action is highly conserved across mammalian species, studying interval timing tasks in animal AD models may be relevant to human disease. Amyloid plaques and tau neurofibrillary tangles are hallmark features of AD. While rodent models of amyloid pathology are known to have interval timing impairments, to our knowledge, interval timing has not been studied in models of tauopathy. Here, we evaluate interval timing performance of P301S transgenic mice, a widely studied model of tauopathy that overexpresses human tau with the P301S mutation. We employed the switch interval timing task, and found that P301S mice consistently underestimated temporal intervals compared to wild-type controls, responding early in anticipation of the target interval. Our study indicating timing deficits in a mouse tauopathy model could have relevance to human tauopathies such as AD. HIGHLIGHTSO_LIWe examined interval timing behavior in mice expressing P301S mutant tau C_LIO_LIP301S mice responded earler than littermate controls C_LIO_LIThese data provide insight into animal models of tauopathy C_LI

neuroscience↗