RESUMO
Michel Jouvet proposed in 1959 that REM sleep is a paradoxical state since it was characterized by the association of a cortical activation similar to wakefulness (W) with muscle atonia. Recently, we showed using cFos as a marker of activity that cortical activation during paradoxical sleep (PS) was limited to a few limbic cortical structures in contrast to W during which all cortices were strongly activated. However, we were not able to demonstrate whether the same neurons are activated during PS and W and to rule out that the activation observed was not linked with stress induced by the flowerpot method of PS deprivation. In the present study, we answered to these two questions by combining tdTomato and cFos immunostaining in the innovative TRAP2 transgenic mice exposed one week apart to two periods of W (W-W mice), PS rebound (PSR-PSR) or a period of W followed by a period of PSR (W-PSR mice). Using such method, we showed that different neurons are activated during W and PSR in the anterior cingulate (ACA) and rostral and caudal retrosplenial (rRSP and cRSP) cortices as well as the claustrum (CLA) previously shown to contain a large number of activated neurons after PSR. Further, the distribution of the neurons during PSR in the rRSP and cRSP was limited to the superficial layers while it was widespread across all layers during W. Our results clearly show at the cellular level that PS and W are two completely different states in term of neocortical activation.
Assuntos
Claustrum/fisiologia , Distúrbios do Sono por Sonolência Excessiva/fisiopatologia , Giro do Cíngulo/fisiologia , Neurônios/fisiologia , Sono REM/fisiologia , Vigília/fisiologia , Animais , Claustrum/citologia , Distúrbios do Sono por Sonolência Excessiva/genética , Distúrbios do Sono por Sonolência Excessiva/patologia , Feminino , Giro do Cíngulo/citologia , Masculino , Camundongos , Camundongos Transgênicos , Polissonografia/métodosRESUMO
To define a protocol of anesthesia for long-duration invasive surgery in a lizard, eight young adult Argentine tegus ( Salvator merianae) of mean body weight 3.0 kg (interquartile range [IQR] 3.40-2.65) were anesthetized with a mixture of ketamine (K) and medetomidine (M) at 19°C, injected intramuscularly and equally distributed in the four limbs. As the experimental surgery procedure required a prolonged deep anesthesia with a good myorelaxation (between 16 and 21 hr), reinjections were required and reflexes were checked during surgery. Times for anesthetic induction, anesthetic reinjection, and recovery periods were recorded for five different combinations of ketamine-medetomidine: 1) 66 mg/kg K + 100 µg/kg M; 2) 80 mg/kg K + 100 µg/kg M; 3) 100 mg/kg K + 130 µg/kg M; 4) 125 mg/kg K + 200 µg/kg M; and 5) 150 mg/kg K + 200 µg/kg M. The effect on the recovery speed of the postoperative atipamezole injection was also evaluated. The median induction time was 30 (IQR 35-27.5) min with no statistical difference between all the concentrations tested. The first reinjection of half a dose was administered after a mean of 5 hr (5.64 hr, IQR 5.95-4.84) as were the subsequent reinjections of a quarter dose (3.99 hr, IQR 5.98-3.23). Intramuscular administration of the ketamine-medetomidine combination is a simple, rapid, and efficient anesthesia for long-term surgery (>12 hr). A mix of 100 mg/kg ketamine and 200 µg/kg medetomidine, with reinjections every 4 hr of half a dose of the previous injection can maintain a good quality of anesthesia for at least 16 hr. The injection of atipamezole after the surgery reverses the effects of medetomidine and permits a reduction of the recovery period.
Assuntos
Anestesia/veterinária , Anestésicos Dissociativos/farmacologia , Hipnóticos e Sedativos/farmacologia , Ketamina/farmacologia , Lagartos/fisiologia , Medetomidina/farmacologia , Anestésicos Dissociativos/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Feminino , Hipnóticos e Sedativos/administração & dosagem , Injeções Intramusculares/veterinária , Ketamina/administração & dosagem , Masculino , Medetomidina/administração & dosagemRESUMO
It is widely accepted that cortical neurons are similarly more activated during waking and paradoxical sleep (PS; aka REM) than during slow-wave sleep (SWS). However, we recently reported using Fos labeling that only a few limbic cortical structures including the retrosplenial cortex (RSC) and anterior cingulate cortex (ACA) contain a large number of neurons activated during PS hypersomnia. Our aim in the present study was to record local field potentials and unit activity from these two structures across all vigilance states in freely moving male rats to determine whether the RSC and the ACA are electrophysiologically specifically active during basal PS episodes. We found that theta power was significantly higher during PS than during active waking (aWK) similarly in the RSC and hippocampus (HPC) but not in ACA. Phase-amplitude coupling between HPC theta and gamma oscillations strongly and specifically increased in RSC during PS compared with aWK. It did not occur in ACA. Further, 68% and 43% of the units recorded in the RSC and ACA were significantly more active during PS than during aWK and SWS, respectively. In addition, neuronal discharge of RSC but not of ACA neurons increased just after the peak of hippocampal theta wave. Our results show for the first time that RSC neurons display enhanced spiking in synchrony with theta specifically during PS. We propose that activation of RSC neurons specifically during PS may play a role in the offline consolidation of spatial memories, and in the generation of vivid perceptual scenery during dreaming.SIGNIFICANCE STATEMENT Fifty years ago, Michel Jouvet used the term paradoxical to define REM sleep because of the simultaneous occurrence of a cortical activation similar to waking accompanied by muscle atonia. However, we recently demonstrated using functional neuroanatomy that only a few limbic structures including the retrosplenial cortex (RSC) and anterior cingulate cortex (ACA) are activated during PS. In the present study, we show for the first time that the RSC and ACA contain neurons firing more during PS than in any other state. Further, RSC neurons are firing in phase with the hippocampal theta rhythm. These data indicate that the RSC is very active during PS and could play a key role in memory consolidation taking place during this state.