Patterns of neural activity in prelimbic cortex neurons correlate with attentional behavior in the rodent continuous performance test

Sustained attention, the ability to focus on a stimulus or task over extended periods, is crucial for higher level cognition, and is impaired across multiple neuropsychiatric and neurodevelopmental disorders, including attention-deficit/hyperactivity disorder, schizophrenia, and depression. The rodent continuous performance test (rCPT) is a translational task that can be used to investigate the cellular mechanisms underlying sustained attention. Electrophysiological single unit and local field potential (LFPs) recordings reflect changes in neural activity in the prelimbic cortex (PrL) in mice performing sustained attention tasks. While evidence linking PrL neuronal activity to sustained attention is compelling, most studies have focused on single-cell activity surrounding behavioral responses, overlooking population-level dynamics across entire sessions that could offer additional insight into fluctuations in attention during task performance. Here, we used in vivo endoscopic calcium imaging to record patterns of neuronal activity in PrL neurons using the genetically encoded calcium sensor GCaMP6f in mice performing the rCPT at three timepoints characterized by differing levels of cognitive demand and task proficiency. We analyzed single-cell activity surrounding behavioral responses and population-level dynamics across sessions to determine how PrL neuronal activity evolves with sustained attention performance. A higher proportion of PrL neurons were recruited during correct responses in sessions requiring high task proficiency. Moreover, during rCPT sessions, mice intercalated responsive-engaged periods with non-responsive-disengaged periods. Applying a Hidden Markov Model (HMM) with two states to global PrL activity, we found neuronal states associated with task engagement. These states are characterized by different levels of correlated neuronal activity within PrL neurons. Overall, these findings illustrate that task proficiency, and task engagement differentially recruit activity in PrL neurons during a sustained attention task.