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International audience; 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.

Based on the rationale that neural hypersynchronization underlies epileptic phenomena, nonperiodic stimulation (NPS) was designed and successfully tested as an electrical stimulus with robust anticonvulsant action. Considering the scale-free temporal structure of NPS mimics natural-like activity, here we hypothesized its application to the amygdala would induce minor to none impairment of neural function in treated animals. Wistar rats underwent gold-standard behavioral tests such as open field (OF), elevated plus-maze (EPM), novel object recognition, and social interaction test in order to evaluate the functions of base-level anxiety, motor function, episodic memory, and sociability. We also performed daily (8 days, 6 h per day) electrophysiological recordings (local field potential/LFP and electromyography) to assess global forebrain dynamics and the sleep-wake cycle architecture and integrity. All animals displayed an increased proportion of time exploring new objects, spent more time in the closed arms of the EPM and in the periphery of the OF arena, with similar numbers of crossing between quadrants and no significant changes of social behaviors. In the sleep-wake cycle electrophysiology experiments, we found no differences regarding duration and proportion of sleep stages and the number of transitions between stages. Finally, the power spectrum of LFP recordings and neurodynamics were also unaltered. We concluded that NPS did not impair neural functions evaluated and thus, it may be safe for clinical studies. Additionally, results corroborate the notion that NPS may exert an on-demand only desynchronization effect by efficiently competing with epileptiform activity for the physiological and healthy recruitment of neural circuitry. Considering the very dynamical nature of circuit activation and functional activity underlying neural function in general (including cognition, processing of emotion, memory acquisition, and sensorimotor integration) and its corruption leading to disorder, such mechanism of action may have important implications in the investigation of neuropsychological phenomena and also in the development of rehabilitation neurotechnology.

Electrical stimulation (ES) of the nervous system is a promising alternative for the treatment of refractory epilepsy. Based on the understanding that seizures are the expression of neural hypersynchronism, our group developed and tested a non-standard form of low-energy temporally unstructured ES termed NPS (Non-periodic stimulation), with pseudo-randomized inter-pulse intervals. Previous investigation demonstrated that NPS applied to the amygdala has a robust anticonvulsant effect against both acute and chronic seizures, and suggested that its therapeutic effect is based on direct desynchronization of ictogenic neural circuits. Further mechanistic investigation using functional magnetic resonance imaging has shown that NPS also activates nucleus accumbens (NAc) in seizure-free rats, raising the hypothesis of an alternative therapeutic mechanism: NPS-enhanced indirect inhibition / desynchronization of ictogenic circuits by NAc. In order to investigate this idea, here we evaluated behavior and cortical electrographic activity from animals submitted to pentylenetetrazole (PTZ) induced seizures, treated with NPS and with or without bilateral electrolytic lesion of NAc. NPS-treated animals with bilateral lesion of NAc expressed unexpected straub tail in addition to other stereotypical convulsive behavior, displayed increased susceptibility to PTZ (lower drug threshold), and had a much longer electrographic seizure, with a greater number of spikes, firing at a higher rate. Moreover, analysis of spike morphology showed an increase in amplitude and slope in these animals, suggesting that ablation of NAc results in disinhibition and/or increase of neural synchronism within ictogenic circuits. NPS had no therapeutic effect whatsoever in lesioned animals, while it displayed a mild anticonvulsant effect in those with intact brains. Results corroborate the notion that NAc has a key role in controlling aberrant epileptiform activity in ictogenic circuits through indirect polysynaptic connections that may enroll the ventral pallidum and ventral tegmental area. They also point to the possibility that NPS may enhance this effect, putatively by benefiting from the structure's property of detecting saliences.

Study Objectives Determine whether in the hippocampus and the supramammillary nucleus (SuM) the same neurons are reactivated when mice are exposed 1 week apart to two periods of wakefulness (W-W), paradoxical sleep rebound (PSR-PSR) or a period of W followed by a period of PSR (W-PSR) Methods We combined the innovative TRAP2 mice method in which neurons expressing cFos permanently express tdTomato after tamoxifen injection with cFos immunohistochemistry. Results We found out that a large number of tdTomato+ and cFos+ cells are localized in the dentate gyrus (DG) after PSR and W while CA1 and CA3 contained both types of neurons only after W. The number of cFos+ cells in the infrapyramidal but not the suprapyramidal blade of the DG was positively correlated with the amount of PS. In addition, we did not find double-labeled cells in the DG whatever the group of mice. In contrast, a high percentage of CA1 neurons were double-labeled in W-W mice. Finally, in the supramammillary nucleus, a large number of cells were double-labeled in W-W, PSR-PSR but not in W-PSR mice. Conclusions Altogether, our results are the first to show that different neurons are activated during W and PS in the supramammillary nucleus and the hippocampus. Further, we showed for the first time that granule cells of the infrapyramidal blade of the DG are activated during PS but not during W. Further experiments are now needed to determine whether these granule cells belong to memory engrams inducing memory reactivation during PS.

Non-periodic stimulation (NPS) has been shown to be an alternative to the treatment of epilepsy due to its anticonvulsant power. In this work, we analyzed the effects of NPS in the amygdalae of animals submitted to pentylenetetrazole (PTZ), a convulsant drug. We used the power spectrum density (PSD) to compare the energy bands and spectral signatures of Wistar rats under the effects of NPS, PTZ, and the use of NPS and PTZ together to characterize each of the agents and to be able to understand therapeutic mechanisms of NPS. All the animals underwent a surgical procedure for implantation of bipolar stimulation electrodes in both amygdalae and of monopolar recording electrodes in thalamus, hippocampus, and cortex. On the experiment day, NPS was applied in the amygdalae of animals in NPS and PTZ + NPS groups. In the PTZ and PTZ + NPS group, animals received a bolus injecion of PTZ (20 mg/Kg). After the experiment, energy bands for the electrophysiologic data were analyzed with Fourier transform performed in a bin with 15 min. Results showed that the spectrum of the PTZ group is deformed to lose energy at lower frequencies ( 100 Hz) when compared with the control group. Animals submitted to PTZ + NPS has a spectral signature with less changes, indicating that NPS acts in a way that forces the PTZ-changed spectrum back to its normal state. Moreover, NPS did not show any effect in the activity of a healthy brain.

A ciencia como empreitada humana de busca do conhecimento muito se beneficiou nao so do estabelecimento do metodo cientifico, mas tambem de sua divulgacao para os pares e para o publico leigo. No fazer cientifico, portanto, entra em cena uma serie de atores para alem do cientista, incluindo o jornalista e outros mais, estando todos eles sujeitos a imprimir, nesse processo, cores de ideologias de toda natureza, inclusive politico-partidaria. Apesar de que a quantidade e a qualidade dessa influencia e discutivel, conhecer o fenomeno parece essencial. Neste artigo de opiniao, apresentamos os elementos basicos do metodo cientifico e da divulgacao cientifica, bem como as relacoes que politica e ciencia mantem, com interesse especial para aquelas que se dao na divulgacao cientifica para o publico leigo. Para isso, analisamos com mais detalhes um caso ilustrativo de influencia de ideologia politico-partidaria na divulgacao leiga da neurociencia: a repercussao na midia eletronica da demonstracao do exoesqueleto robotico na abertura da Copa do Mundo no Brasil. Concluimos com reflexoes sociologicas que situam a questao em analise em uma perspectiva que talvez coopere na importante aproximacao entre ciencia e jornalismo