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Electrophysiological correlates of attention in the locus coeruleus–prelimbic cortex circuit during the rodent continuous performance test

Neuropsychopharmacology volume 49, pages 521–531 (2024)Cite this article

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Abstract

Sustained attention, the ability to focus on an activity or stimulus over time, is significantly impaired in many psychiatric disorders, and there remains a major unmet need in treating impaired attention. Continuous performance tests (CPTs) were developed to measure sustained attention in humans, non-human primates, rats, and mice, and similar neural circuits are engaged across species during CPT performance, supporting their use in translational studies to identify novel therapeutics. Here, we identified electrophysiological correlates of attentional performance in a touchscreen-based rodent CPT (rCPT) in the locus coeruleus (LC) and prelimbic cortex (PrL), two inter-connected regions that are implicated in attentional processes. We used viral labeling and molecular techniques to demonstrate that neural activity is recruited in LC-PrL projections during the rCPT, and that this recruitment increases with cognitive demand. We implanted male mice with depth electrodes within the LC and PrL for local field potential (LFP) recordings during rCPT training, and identified an increase in PrL delta and theta power, and an increase in LC delta power during correct responses in the rCPT. We also found that the LC leads the PrL in theta frequencies during correct responses while the PrL leads the LC in gamma frequencies during incorrect responses. These findings may represent translational biomarkers that can be used to screen novel therapeutics for drug discovery in attention.

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Fig. 1: rCPT training recruits PrL-projecting LC neurons.
Fig. 2: LFP recording sessions within rCPT training stages.
Fig. 3: Correct responses (hits) during Stage 3 of rCPT training increase delta and theta power within the PrL.
Fig. 4: Correct responses during Stage 3-late of rCPT training increase delta power within the LC.
Fig. 5: LC leads PrL in theta and beta frequencies during hits in Stage 3-late.

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Acknowledgements

We thank members of the Martinowich and Carr laboratories for helpful comments and suggestions. We also thank Aimee Ormond and Deveren Manley for assistance with animal care.

Funding

This work was supported by internal funding from the Lieber Institute for Brain Development, and the National Institute of Mental Health (R01MH105592 to KM; R56MH126233 to GVC and KM).

Author information

Author notes

  1. These authors contributed equally: Henry L. Hallock, Suhaas S. Adiraju.

  2. These authors jointly supervised this work: Gregory V. Carr, Keri Martinowich.

Authors and Affiliations

  1. Neuroscience Program, Lafayette College, Easton, PA, 18042, USA

    Henry L. Hallock

  2. Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA

    Suhaas S. Adiraju, Jorge Miranda-Barrientos, Jessica M. McInerney, Seyun Oh, Adrienne C. DeBrosse, Ye Li, Gregory V. Carr & Keri Martinowich

  3. Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Gregory V. Carr

  4. Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA

    Keri Martinowich

  5. Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA

    Keri Martinowich

  6. The Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD, 21205, USA

    Keri Martinowich

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Contributions

Conceptualization: HLH, GVC, and KM. Methodology: HLH, JMM, JMB, SSA, ACD, and YL. Validation: JMB and SO. Formal analysis: HLH and SSA. Investigation: HLH, SSA, JMB, JMM, and SO. Data curation: HLH, SA, and JMB. Writing—original draft: HLH, SSA, JMB, GVC, and KM. Writing—review and editing: HLH, SSA, JMB, GVC, and KM. Visualization: HLH, SSA, and JMB. Supervision: HLH, JMB, and KM. Project administration: JMB, KM, and GVC. Funding acquisition: GVC and KM.

Corresponding authors

Correspondence to Gregory V. Carr or Keri Martinowich.

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Competing interests

KM is the Social Media Editor for Neuropsychopharmacology. GVC is a scientific advisor for LongTermGevity, Inc. and owns stock options in the company. LongTermGevity, Inc. was not involved in the funding, design, or execution of these studies. No other authors have financial relationships with commercial interests, and the authors declare no competing interests.

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Hallock, H.L., Adiraju, S.S., Miranda-Barrientos, J. et al. Electrophysiological correlates of attention in the locus coeruleus–prelimbic cortex circuit during the rodent continuous performance test. Neuropsychopharmacol. 49, 521–531 (2024). https://doi.org/10.1038/s41386-023-01692-3

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