Biology subjects

Rehg, J. J.

Publications and source records attributed to Rehg, J. J..

3 recordsLinked to original sources

bioRxiv2025

Top-down control of sustained attention by the medial prefrontal cortex (mPFC)- locus coeruleus (LC) circuit during the rodent continuous performance task (rCPT)

The medial prefrontal cortex (mPFC) plays a pivotal role in attention by exerting top-down control to allocate cognitive resources toward behaviorally relevant stimuli based on learned context and expectations. mPFC neurons project to multiple cortical and subcortical regions, including the locus coeruleus (LC)--the brains primary source of norepinephrine (NE). The mPFC also receives inputs from the LC, which release NE to modulate mPFC neuronal activity and downstream cellular signaling. While enhanced functional connectivity between the mPFC and LC in mice during sustained attention tasks suggest an important role for the mPFC-LC circuit, functional evidence directly implicating this circuit in attention is lacking. Here, we investigated the role of the mPFC-LC circuit in attention by comparing selective chemogenetic manipulation of mPFC neurons that project to the LC (mPFC-LC projectors) to non-specific chemogenetic manipulation of mPFC neurons. Selective activation of mPFC-LC projectors in mice performing the rodent continuous performance test (rCPT), a translational sustained attention task, robustly improves attentional performance by enhancing discrimination while non-selective activation of mPFC neurons increases attentional performance by increasing responsiveness. Behavioral effects of mPFC-LC projector activation were mediated by recruitment of a microcircuit involving LC-NE neurons and glutamate and GABA peri-LC neurons while effects of non-selective activation of mPFC neurons were mediated by engaging downstream targets such as the nucleus accumbens (NAc) as well as the LC/peri-LC region.

neuroscience↗

bioRxiv2024

Time-on-task-related decrements in performance in the rodent continuous performance test are not caused by physical disengagement from the task

Attention deficits, a hallmark of many neuropsychiatric disorders, significantly impair quality of life and functional outcome for patients. Continuous Performance Tests (CPTs) are widely used to assess attentional function in clinical settings and have been adapted for mice as the rodent Continuous Performance Test (rCPT). In this study, we combined traditional analyses of rCPT performance with markerless pose estimation using DeepLabCut and visual field analysis (VFA) to objectively measure the orientation of mice toward stimuli during rCPT sessions. Additionally, we extended session lengths to assess performance decrements over time. Our findings show that extending rCPT sessions from 45 to 90 minutes results in a significant decline in performance in male mice, which aligns with performance decrements observed in clinical research. Importantly, physical engagement with the task remained relatively stable throughout the session, even as performance deteriorated. This suggests that the performance decline specifically reflects a time-on-task (TOT)-dependent vigilance decrement rather than physical disengagement. We also investigated the effects of amphetamine, an FDA-approved treatment for attention-deficit/hyperactivity disorder (ADHD), on rCPT performance. Amphetamine significantly improved rCPT performance in male mice by reducing false alarms without modulating orientation or physical engagement with the task stimuli. Collectively, these findings validate a behavioral tracking platform for objectively measuring physical engagement in the rCPT and a task modification that accentuates TOT-dependent performance decrements, enhancing the translational value of the rCPT for studies related to human neuropsychiatric disorders.

neuroscience↗

bioRxiv2024

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.

neuroscience↗