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

We traced the changes in GABAergic parvalbumin (PV)-expressing interneurons of the hippocampus and reticulo-thalamic nucleus (RT) as possible underlying mechanisms of the different local cortical and hippocampal electroencephalographic (EEG) microstructures during the non-rapid-eye movement (NREM) sleep compared with anesthesia-induced unconsciousness by two anesthetics with different main mechanisms of action (ketamine/diazepam versus propofol). After 3 h of recording their sleep, the rats were divided into two experimental groups: one half received ketamine/diazepam anesthesia and the other half received propofol anesthesia. We simultaneously recorded the EEG of the motor cortex and hippocampus during sleep and during 1 h of surgical anesthesia. We performed immunohistochemistry and analyzed the PV and postsynaptic density protein 95 (PSD-95) expression. PV suppression in the hippocampus and at RT underlies the global theta amplitude attenuation and hippocampal gamma augmentation that is a unique feature of ketamine-induced versus propofol-induced unconsciousness and NREM sleep. While PV suppression resulted in an increase in hippocampal PSD-95 expression, there was no imbalance between inhibition and excitation during ketamine/diazepam anesthesia compared with propofol anesthesia in RT. This increased excitation could be a consequence of a lower GABA interneuronal activity and an additional mechanism underlying the unique local EEG microstructure in the hippocampus during ketamine/diazepam anesthesia.

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

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.

Prodromal local sleep disorders in a rat model of Parkinson's disease cholinopathy, hemiparkinsonism and hemiparkinsonism with cholinopathy.

We investigated the prodromal alterations of local sleep, particularly the motor cortical and hippocampal sleep, along with spontaneous locomotor activity in the rat models of Parkinson's disease (PD). We performed our experiments in adult, male Wistar rats, chronically implanted for sleep recording and divided into four experimental groups: the control (implanted controls), the bilateral pedunculopontine tegmental nucleus (PPT) lesions (PD cholinopathy), the unilateral substantia nigra pars compacta (SNpc) lesions (hemiparkinsonism) and the unilateral SNpc/bilateral PPT lesions (hemiparkinsonism with PD cholinopathy). We followed their sleep, basal locomotor activity and spatial habituation for 14 days following the surgical procedures. Severe prodromal local sleep disturbances in the hemiparkinsonian rats were expressed as sleep fragmentation and distinct local NREM/REM EEG microstructure alterations in both the motor cortex and the hippocampus. Alongside the state-unrelated role of the dopaminergic control of theta oscillations and NREM/REM related sigma and beta oscillations, we demonstrated that the REM neurochemical regulatory substrate is particularly important in the dopaminergic control of beta oscillations. In addition, hippocampal prodromal sleep disorders in the hemiparkinsonian rats were expressed as NREM/REM fragmentation and the opposite impact of dopaminergic versus cholinergic control of the NREM delta and beta oscillation amplitudes in the hippocampus, likewise in the motor cortex versus the hippocampus. All these distinct prodromal local sleep disorders and the dopaminergic vs. cholinergic impact on NREM/REM EEG microstructure alterations are of fundamental importance for the further development and follow-up of PD-modifying therapies, and for the identification of patients who are at risk of developing PD.

Diversity of simultaneous sleep in the motor cortex and hippocampus in rats.

We investigated the homogeneity/heterogeneity of spontaneous sleep, simultaneously recorded in the motor cortex and the hippocampus of control rats, and particularly analysed simultaneous and non-simultaneous motor cortical and hippocampal non-rapid eye movement (NREM)/rapid eye movement (REM) sleep. We demonstrate that the sleep architectures of the motor cortex and hippocampus are different in control rats. There was an increase of NREM duration and a decrease of REM duration in the hippocampus versus the motor cortex. In terms of duration, NREM state is the most heterogeneous in the hippocampus, whereas the REM state is the most heterogeneous in the motor cortex. Whereas the hippocampal NREM duration was increased due to the prolongation of NREM episodes, the hippocampal REM duration decreased due to the decreased number of REM episodes. The heterogeneity of sleep in the motor cortex and hippocampus in control rats was particularly expressed through the inverse alteration of sigma amplitude during NREM sleep and beta/gamma amplitudes during REM sleep in the hippocampus, along with the delta, sigma, beta and gamma amplitudes only during non-simultaneous NREM/REM sleep in the hippocampus. We demonstrated the brain structure-related and NREM/REM state-related heterogeneity of the motor cortical and hippocampal local sleep in control rats. The distinctly altered local NREM/REM states, alongside their episode dynamics and electroencephalographic (EEG) microstructures, suggest the importance of both the local neuronal network substrate and the NREM/REM neurochemical substrate in the control mechanisms of sleep.