Behavioural Brain Research 256 (2013) 108–118 Contents lists available at ScienceDirect Behavioural Brain Research j ourna l h o mepa ge: www.elsevier.com/locate/bbr Research report Topography of the sleep/wake states related EEG microstructure and transitions structure differentiates the functionally distinct cholinergic innervation disorders in rat Jelena Petrovic a , Katarina Lazic a , Jelena Ciric 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 • We used the rat models of the cholinergic neuronal innervation disorders. • Bilateral NB or PPT lesions were done by ibotenic acid microinfusion. • We investigated the impact of lesions during sleep. • NB and PPT lesions are differently expressed in sensorimotor vs. motor cortex. • Differing EEG microstructure and transition structure are the hallmarks of lesions. a r t i c l e i n f o Article history: Received 24 June 2013 Received in revised form 22 July 2013 Accepted 26 July 2013 Available online xxx Keywords: Nucleus basalis Pedunculopontine tegmental nucleus Ibotenic acid Lesion Cholinergic neurons a b s t r a c t In order to identify the differences for the onset and progression of functionally distinct cholinergic innervation disorders, we investigated the effect of bilateral nucleus basalis (NB) and pedunculopontine tegmental nucleus (PPT) lesions on sleep/wake states and electroencephalographic (EEG) microstructure in rats, chronically implanted for sleep recording. Bilateral NB lesion transiently altered Wake/NREM duration within the sensorimotor cortex, and Wake/REM duration within the motor cortex, while there was no change in the sleep/wake states distributions following the bilateral PPT lesion. Bilateral PPT lesion sustainably increased the Wake/REM and REM/Wake transitions followed by inconsistent dysregulation of the NREM/REM and REM/NREM transitions in sensorimotor cortex, but oppositely by their increment throughout four weeks in motor cortex. Bilateral NB lesion sustainably decreased the NREM/REM and REM/NREM transitions during four weeks in the sensorimotor cortex, but oppositely increased them in the motor cortex. We have shown that the sustained beta and gamma augmentation within the sensorimotor and motor cortex, and across all sleep/wake states, simultaneously with Wake delta amplitude attenu- ation only within the sensorimotor cortex, were the underlying EEG microstructure for the sleep/wake states transitions structure disturbance following bilateral PPT lesion. In contrast, the bilateral NB lesion only augmented REM theta in sensorimotor cortex during three weeks. We have shown that the NB and PPT lesions induced differing, structure-related EEG microstructure and transition structure disturbances particularly expressed in motor cortex during NREM and REM sleep. We evidenced for the first time the different topographical expression of the functionally distinct cholinergic neuronal innervation impairment in rat. © 2013 Elsevier B.V. All rights reserved. 1. Introduction Human development, maturation, healthy aging [1,2], and many neurological diseases [3] are associated with a variety of the ∗ 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 address: jasnasap@ibiss.bg.ac.rs (J. Saponjic). sleep-related behavioral disorders. Neurodegenerative diseases, such as Alzheimer’s (AD) and Parkinson’s (PD) diseases, involve the selective loss of specific neuronal populations within the brain [4,5]. In addition, regarding the cholinergic neuronal loss, while AD involves selective loss of the basal forebrain cholinergic system, PD is related to the selective loss of the pontine cholinergic system [6,7]. Moreover, AD has been characterized as a “disorder of corti- cal cholinergic innervation” [8]. The REM sleep behavior disorder (RBD), reflecting an underlying synucleinopathy with ascending pattern of the neurodegeneration, precedes as a symptom the 0166-4328/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.bbr.2013.07.047