Hippocampal sleep spindle dynamics during REM sleep and their distinct underlying parvalbumin and synaptic proteins expression in the reticulo-thalamic nucleus of the parkinsonian rats

Abstract

We investigated the alterations of reticulo-thalamic (RT) GABAergic parvalbumin (PV+) interneurons and synaptic reorganization underlying the altered hippocampal high voltage sleep spindle (HVS) dynamics during REM sleep in the rat models of Parkinson’s disease (PD). Adult male Wistar rats were implanted for 6h sleep recording during light phase in four experimental groups: control (implanted controls), PD cholinopathy (bilateral lesion of the nucleus pedunculopontinus tegmentalis−PPT), hemiparkinsonism (unilateral lesion of the nucleus substantiae nigrae pars compacta−SNpc) and hemiparkinsonism with PD cholinopathy (unilateral SNpc/bilateral PPT lesion). Following 14 days of the surgical procedure we differentiated the Wake/NREM/REM 10s epochs, and the HVSs detection and extraction was done automatically (4.1–10 Hz band pass filter, 1s minimum duration) and visually validated. Hippocampal HVS dynamics were analyzed during 1h of NREM/REM sleep. Alterations of the PV+ interneurons and synaptic re-organization within the RT were determined by the parvalbumin, MAP2 and PSD-95 immunostaining. REM sleep is a predisposing state for the HVSs induction in all experimental models of PD neuropathology. Whereas the PD cholinopathy induced the prolongation and higher density of hippocampal HVSs, the hemiparkinsonism with PD cholinopathy increased the hippocampal HVSs intrinsic frequency during REM sleep. In contrast to the unaltered PV+ interneurons/partially enhanced MAP2/suppressed PSD-95 expression during PD cholinopathy, we evidenced the PV+ interneurons reduction/enhanced MAP2/no change of PSD-95 expression in the RT during hemiparkinsonism with PD cholinopathy. Distinct PV+ interneurons alteration and inhibition/excitation balance in the RT could be the underlying mechanisms of HVS generation/alteration during REM sleep in the parkinsonian rats.