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Cholinergic Oculomotor Nucleus Activity Is Induced by REM Sleep Deprivation Negatively Impacting on Cognition

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Abstract

Several efforts have been made to understand the involvement of rapid eye movement (REM) sleep for cognitive processes. Consolidation or retention of recognition memories is severely disrupted by REM sleep deprivation (REMSD). In this regard, pedunculopontine tegmental nucleus (PPT) and other brainstem nuclei, such as pontine nucleus (Pn) and oculomotor nucleus (OCM), appear to be candidates to take part in this REM sleep circuitry with potential involvement in cognition. Therefore, the objective of this study was to investigate a possible association between the performance of Wistar rats in a declarative memory and PPT, Pn, and OCM activities after different periods of REMSD. We examined c-Fos and choline acetyltransferase (ChaT) expressions as indicators of neuronal activity as well as a familiarity-based memory test. The animals were distributed in groups: control, REMSD, and sleep rebound (REB). At the end of the different REMSD (24, 48, 72, and 96 h) and REB (24 h) time points, the rats were immediately tested in the object recognition test and then the brains were collected. Results indicated that OCM neurons presented an increased activity, due to ChaT-labeling associated with REMSD that negatively correlated (r = −0.32) with the cognitive performance. This suggests the existence of a cholinergic compensatory mechanism within the OCM during REMSD. We also showed that 24 h of REMSD impacted similarly in memory, compared to longer periods of REMSD. These data extend the notion that REM sleep is influenced by areas other than PPT, i.e., Pn and OCM, which could be key players in both sleep processes and cognition.

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Abbreviations

ChaT:

Choline acetyltransferase

DI:

Discrimination index

OCM:

Oculomotor nucleus

PD:

Parkinson’s disease

PPT:

Pedunculopontine tegmental nucleus

Pn:

Pontine nucleus

REM:

Rapid eye movement

REMSD:

REM sleep deprivation

REB:

Rebound

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Acknowledgments

This paper was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq—Brasil Grants Casadinho/Procad no. 552226/2011-4 and Universal no. 473861/2012-7 to MMSL. MMSL is recipient of CNPq fellowship.

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Authors and Affiliations

  1. Laboratório de Neurofisiologia, Departamento de Fisiologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Av. Francisco H. dos Santos s/n, Caixa Postal: 19031, Curitiba, Paraná, 81.531-990, Brazil

    Patrícia Dos Santos, Adriano D. S. Targa, Ana Carolina D. Noseda, Lais S. Rodrigues, Juliane Fagotti & Marcelo M. S. Lima

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  1. Patrícia Dos Santos
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  2. Adriano D. S. Targa
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  3. Ana Carolina D. Noseda
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  4. Lais S. Rodrigues
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  5. Juliane Fagotti
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  6. Marcelo M. S. Lima
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Corresponding author

Correspondence to Marcelo M. S. Lima.

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Ethics Statement

The studies were carried out in accordance with the guidelines of the Committee on the Care and Use of Laboratory Animals, US National Institutes of Health. In addition, the protocol complies with the recommendations of Federal University of Paraná and was approved by the Institutional Ethics Committee (approval ID no. 759).

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The authors declare that they have no conflict of interests.

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Santos, P.D., Targa, A.D.S., Noseda, A.C.D. et al. Cholinergic Oculomotor Nucleus Activity Is Induced by REM Sleep Deprivation Negatively Impacting on Cognition. Mol Neurobiol 54, 5721–5729 (2017). https://doi.org/10.1007/s12035-016-0112-z

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