Hippocampal and Reticulo-Thalamic Parvalbumin Interneurons and Synaptic Re-Organization during Sleep Disorders in the Rat Models of Parkinson’s Disease Neuropathology

Abstract

We investigated the alterations of hippocampal and reticulo-thalamic (RT) GABAergic parvalbumin (PV) interneurons and their synaptic re-organizations underlying the prodromal local sleep disorders in the distinct rat models of Parkinson’s disease (PD). We demonstrated for the first time that REM sleep is a predisposing state for the high-voltage sleep spindles (HVS) induction in all experimental models of PD, particularly during hippocampal REM sleep in the hemiparkinsonian models. There were the opposite underlying alterations of the hippocampal and RT GABAergic PV+ interneurons along with the distinct MAP2 and PSD-95 expressions. Whereas the PD cholinopathy enhanced the number of PV+ interneurons and suppressed the MAP2/PSD-95 expression, the hemiparkinsonism with PD cholinopathy reduced the number of PV+ interneurons and enhanced the MAP2/PSD-95 expression in the hippocampus. Whereas the PD cholinopathy did not alter PV+ interneurons but partially enhanced MAP2 and suppressed PSD-95 expression remotely in the RT, the hemiparkinsonism with PD cholinopathy reduced the PV+ interneurons, enhanced MAP2, and did not change PSD-95 expression remotely in the RT. Our study demonstrates for the first time an important regulatory role of the hippocampal and RT GABAergic PV+ interneurons and the synaptic protein dynamic alterations in the distinct rat models of PD neuropathology.

Different Alterations of Hippocampal and Reticulo-Thalamic GABAergic Parvalbumin-Expressing Interneurons Underlie Different States of Unconsciousness

“…Surgical procedures for chronic electrode implantation for sleep recording were performed as previously described [ 43 , 44 , 45 , 46 ].…”

“…Sleep was recorded for 3 h during the light phase, starting at 09:00 a.m. EEG and EMG activities were recorded differentially. After conventional amplification and filtering (0.3–100 Hz bandpass; A-M System Inc. model 3600, Carlsborg, WA, USA), the analog data were digitized (at a sampling rate of 256/s) using DataWave SciWorks Experimenter version 11.2 (A-M System, Carlsborg, WA, USA), and the EEG and EMG activities were displayed on a computer monitor and stored on a hard disk for further offline analysis [ 43 , 44 , 45 , 46 ]. After 3 h of sleep recording, the rats were anesthetized with ketamine/diazepam (100 mg/kg, Zoletil ® 50, VIRBAC, France) or propofol (100 mg/kg; Propofol Lipuro 2% (20 mg/mL), B. BRAUN ADRIA RSRB d.o.o., Belgrade, Serbia) and we simultaneously recorded EEGs of the motor cortex and hippocampus during 1 h of stable surgical stage of both anesthetics.…”

“…All of the EEG analyses were performed in MATLAB R2011a (MathWorks Inc., Natick, MA, USA) using software originally developed in MATLAB 6.5 [ 43 , 44 , 45 , 46 , 48 ]. The EEG analysis of the individual states of unconsciousness included only the artifact-free recorded signals.…”

“…The EEG analysis of the individual states of unconsciousness included only the artifact-free recorded signals. In this study, we applied the FFT algorithm to the signals acquired during each 3 h sleep recording (a total of 1080 10 s Fourier epochs) and automatically differentiated each 10 s epoch as a waking state, NREM state, or REM state [ 44 , 45 , 46 , 48 ]. Specifically, to assess local NREM sleep, we extracted 30 min of simultaneous NREM sleep (a total of 180 simultaneous NREM 10 s epochs from motor cortex and hippocampus), obtained from previously defined total simultaneous NREM sleep of the motor cortex and hippocampus, extracted always from the first and the second hour of all sleep recordings [ 43 , 44 , 46 ].…”

“…In this study, we applied the FFT algorithm to the signals acquired during each 3 h sleep recording (a total of 1080 10 s Fourier epochs) and automatically differentiated each 10 s epoch as a waking state, NREM state, or REM state [ 44 , 45 , 46 , 48 ]. Specifically, to assess local NREM sleep, we extracted 30 min of simultaneous NREM sleep (a total of 180 simultaneous NREM 10 s epochs from motor cortex and hippocampus), obtained from previously defined total simultaneous NREM sleep of the motor cortex and hippocampus, extracted always from the first and the second hour of all sleep recordings [ 43 , 44 , 46 ]. Then, we analyzed the local NREM sleep EEG microstructure by calculating the relative NREM amplitudes of all conventional EEG frequency bands (δ = 0.3–4 Hz; θ = 4.1–8 Hz; σ = 10.1–15 Hz; β = 15.1–30 Hz; γ = 30.1–50 Hz) [ 43 , 44 , 45 ].…”