Behavioural Brain Research 271 (2014) 258–268 Contents lists available at ScienceDirect Behavioural Brain Research jou rn al hom epage: www.elsevier.com/locate/bbr Research report REM sleep diversity following the pedunculopontine tegmental nucleus lesion in rat Jelena Petrovic a , Katarina Lazic a , Aleksandar Kalauzi b , Jasna Saponjic a,∗ a University of Belgrade, Department of Neurobiology, Institute for Biological Research – Sinisa Stankovic, 11 060 Belgrade, Serbia b University of Belgrade, Department for Life Sciences, Institute for Multidisciplinary Research, 11 030 Belgrade, Serbia h i g h l i g h t s • Pedunculopontine tegmental nucleus (PPT) is a source of thalamo-cortical innervation. • PPT cholinergic neuronal loss potentiated the emergence of two REM sleep states. • Pathological REM1 and REM2 have differential total EMG power. • REM1 and REM2 have topographically distinct EEG microstructures. • REM1 and REM2 have distinct cortical drive to dorsal nuchal musculature. a r t i c l e i n f o Article history: Received 22 April 2014 Received in revised form 9 June 2014 Accepted 10 June 2014 Available online 17 June 2014 Keywords: REM sleep The pedunculopontine tegmental nucleus Excitotoxic lesion EEG EMG Cortico-muscular coherence a b s t r a c t The aim of this study was to demonstrate that two REM clusters, which emerge following bilateral pedunculopontine tegmental nucleus (PPT) lesions in rats, are two functionally distinct REM states. We performed the experiments in Wistar rats, chronically instrumented for sleep recording. Bilateral PPT lesions were produced by the microinfusion of 100 nl of 0.1 M ibotenic acid (IBO). Following a recovery period of 2 weeks, we recorded their sleep for 6 h. Bilateral PPT lesions were identified by NADPH – diaphorase histochemistry. We applied Fourier analysis to the signals acquired throughout the 6 h recordings, and each 10 s epoch was differentiated as a Wake, NREM or REM state. We analyzed the topography of the sleep/wake states architecture and their transition structure, their all state-related EEG microstructures, and the sensorimotor (SMCx) and motor (MCx) cortex REM related cortico-muscular coherences (CMCs). Bilateral PPT lesion in rats increased the likelihood of the emergence of two distinct REM sleep states, specifically expressed within the MCx: REM1 and REM2. Bilateral PPT lesion did not change the sleep/wake states architecture of the SMCx, but pathologically increased the duration of REM1 within the MCx, alongside increasing Wake/REM1/Wake and NREM/REM2/NREM transitions within both cortices. In addition, the augmented total REM SMCx EEG beta amplitude and REM1 MCx EEG theta amplitude was the underlying EEG microstructure pathology. PPT lesion induced REM1 and REM2 are differential states with regard to total EMG power, topograph- ically distinct EEG microstructures, and locomotor drives to nuchal musculature. © 2014 Elsevier B.V. All rights reserved. 1. Introduction REM sleep behavioral disorder (RBD) is a unique parasom- nia characterized by the loss of normal skeletal muscle atonia ∗ Corresponding author at: University of Belgrade, Department of Neurobiology, Institute for Biological Research – Sinisa Stankovic, Despot Stefan Blvd., 142, 11060 Belgrade, Serbia. Tel.: +381 11 2078426; fax: +381 11 2761433. E-mail addresses: jasnasaponjic@yahoo.com, jasnasap@ibiss.bg.ac.rs (J. Saponjic). and dream enactment behavior during REM sleep. Although RBD can be triggered pharmacologically [1], it is generally related to structural lesions within the midbrain and pontomedullary brain- stem, with consequent uninhibited control of the motor cortex relating to limbs, most likely bypassing basal ganglia or other modulatory structures [1–4]. In humans RBD can be associated with pontomedullary strokes [2], narcolepsy, limbic encephali- tis, Gullain-Barre syndrome, pharmacological agents (tricyclic or serotonergic antidepressants, alcohol, and beta blockers), and with a range of neurodegenerative diseases, including progres- sive supranuclear palsy, corticobasal syndrome, frontotemporal http://dx.doi.org/10.1016/j.bbr.2014.06.026 0166-4328/© 2014 Elsevier B.V. All rights reserved.