No description available.

The pedunculopontine tegmental (PPT) nucleus is a brainstem structure thought to be important in the regulation of sleep/wake states. The PPT is comprised of three distinct types of neurons (cholinergic, GABAergic, and glutamatergic), and each may serve different functions. It remains unknown how PPT neurons affect specific sleep/wake states and which of their axonal projections mediate their effect. Therefore, we used optogenetics to selectively activate glutamatergic PPT (PPTglut) neurons at both the cell soma and axon terminals in a temporally and spatially precise manner. The purpose of these experiments was to determine the role of PPTglut neurons during wake, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep, and to identify the key projections through which PPTglut neurons produce their effects. Using transgenic mice, we transfected PPTglut neurons with an adeno-associated viral vector to induce expression of a light-dependent ion channel, channelrhodopsin-2 (ChR2). While recording electroencephalography (EEG), electromyography (EMG), and video feed, we photostimulated the transfected PPTglut neurons and measured the effects on sleep/wake states of the mice. Stimulation of the PPTglut soma during NREM sleep produced a frequency-dependent wake response. With increasing frequency of stimulation, we observed an increase in the speed of the wake response, as well as the amplitude and duration of the wake response. Stimulating the PPTglut soma increased time spent in wake, decreased NREM sleep, and slightly decreased REM sleep. We also noticed that mice did not exhibit spontaneous body movements during stimulation of the PPTglut soma. Stimulating individual PPTglut axon terminal fields partially recapitulated the phenotype observed with stimulation of the cell soma. Photostimulation of axon terminals in the basal forebrain, lateral hypothalamus, and thalamus elicited a fast wake response, stimulation of both the basal forebrain and lateral hypothalamus terminal fields produced a strong wake response, but long-lasting wakefulness was observed only with high-frequency stimulation of axon terminals in the lateral hypothalamus. In summary, photostimulation of PPTglut neurons promotes wake, and slightly decreases REM sleep. Our experiments strongly support the role of PPTglut neurons in promoting wakefulness from NREM sleep, and this wake response is carried out through several axonal projections which, in sum, recapitulate the wake phenotype observed with stimulation of the cell soma in the PPT itself. Further exploration of the axonal projections of PPTglut neurons is warranted to elucidate the neuronal targets through which this response is carried out. / 2019-07-03T00:00:00Z

Estrutura central do hipocampo, o corno de Ammon pode ser subdividido em pelo menos três áreas: CA1, CA2 e CA3. Enquanto CA1 e CA3 foram extensamente estudados, dado o envolvimento do hipocampo em processos cognitivos como a memória e patológicos como a epilepsia, CA2 tem sido largamente ignorado na literatura. Entretanto, este campo possui características específicas, tanto neuroanatômicas como bioquímicas e fisiológicas, sendo resistente à indução de plasticidade e recebendo aferência específica do núcleo supramamilar do hipotálamo, envolvido na circuitaria geradora/mantenedora do ritmo teta, oscilações centrais ao funcionamento do hipocampo. O objetivo deste estudo foi, portanto, caracterizar no animal em livre movimentação os padrões de atividade eletrofisiológica nas três áreas do corno de Ammon bilateralmente. Os resultados demonstraram que CA2 possui, em média, intervalos entre disparos mais prolongados que CA1 e CA3 durante o sono de ondas lentas e o sono REM. Nestas fases do ciclo a coerência entre CA1-CA2 foi mais elevada que entre CA1-CA3 e CA2-CA3 nos três ratos avaliados, em três faixas de freqüência: teta (6 a 12 Hz), gama lento (30 a 50 Hz) e gama rápido (90 a 110 Hz) ipsilateralmente. A coerência entre campos contralaterais é predominante no teta, sendo quase zero nas demais freqüências. Estes resultados corroboram trabalhos recentes que apontam CA2 como área distinta e sugerem que esta pequena região do corno de Ammon possa exercer papéis importantes na modulação da atividade das demais estruturas hipocampais e parahipocampais em processos de memória e em patologias como a epilepsia / The Ammons horn, central structure of the hippocampus, can be subdivided in at least three regions: CA1, CA2 and CA3. While CA1 and CA3 have been extensively studied given the hippocampus involvement in cognitive processes such as memory and pathological ones such as epilepsy, CA2 remains largely ignored. However, this sector contains specific neuroanatomical, biochemical e physiological characteristics, being resistant to induction of plasticity and receiving a specific afference from the supramammillary nucleus in the hypothalamus, involved in the generation/maintenance of the theta rhythm, central oscillations to hippocampal functioning. Therefore, the objective of this study was to characterize electrophysiological patterns of interaction in the three areas of the Ammons horn bilaterally. Results revealed that CA2 has a mean interspike interval larger than CA1 and CA3 during slow wave and REM sleep. During these stages of the sleep-wake cycle, coherence between CA1-CA2 was higher than CA1-CA3 and CA2-CA3 in the three animals evaluated, in three frequency bands: theta (6 to 12 Hz), slow gamma (30 to 50 Hz) and fast gamma (90 to 110 Hz) ipsilaterally. Coherence between contralateral fields was predominant in the theta band and almost zero in other frequencies. These results add to some previous published data showing that CA2 is distinct from the other subfields and that this small region of the Ammons horn may exert important roles in modulating activity in the other hippocampal fields and parahippocampal regions during memory and pathologies such as epilepsy

Estrutura central do hipocampo, o corno de Ammon pode ser subdividido em pelo menos três áreas: CA1, CA2 e CA3. Enquanto CA1 e CA3 foram extensamente estudados, dado o envolvimento do hipocampo em processos cognitivos como a memória e patológicos como a epilepsia, CA2 tem sido largamente ignorado na literatura. Entretanto, este campo possui características específicas, tanto neuroanatômicas como bioquímicas e fisiológicas, sendo resistente à indução de plasticidade e recebendo aferência específica do núcleo supramamilar do hipotálamo, envolvido na circuitaria geradora/mantenedora do ritmo teta, oscilações centrais ao funcionamento do hipocampo. O objetivo deste estudo foi, portanto, caracterizar no animal em livre movimentação os padrões de atividade eletrofisiológica nas três áreas do corno de Ammon bilateralmente. Os resultados demonstraram que CA2 possui, em média, intervalos entre disparos mais prolongados que CA1 e CA3 durante o sono de ondas lentas e o sono REM. Nestas fases do ciclo a coerência entre CA1-CA2 foi mais elevada que entre CA1-CA3 e CA2-CA3 nos três ratos avaliados, em três faixas de freqüência: teta (6 a 12 Hz), gama lento (30 a 50 Hz) e gama rápido (90 a 110 Hz) ipsilateralmente. A coerência entre campos contralaterais é predominante no teta, sendo quase zero nas demais freqüências. Estes resultados corroboram trabalhos recentes que apontam CA2 como área distinta e sugerem que esta pequena região do corno de Ammon possa exercer papéis importantes na modulação da atividade das demais estruturas hipocampais e parahipocampais em processos de memória e em patologias como a epilepsia / The Ammons horn, central structure of the hippocampus, can be subdivided in at least three regions: CA1, CA2 and CA3. While CA1 and CA3 have been extensively studied given the hippocampus involvement in cognitive processes such as memory and pathological ones such as epilepsy, CA2 remains largely ignored. However, this sector contains specific neuroanatomical, biochemical e physiological characteristics, being resistant to induction of plasticity and receiving a specific afference from the supramammillary nucleus in the hypothalamus, involved in the generation/maintenance of the theta rhythm, central oscillations to hippocampal functioning. Therefore, the objective of this study was to characterize electrophysiological patterns of interaction in the three areas of the Ammons horn bilaterally. Results revealed that CA2 has a mean interspike interval larger than CA1 and CA3 during slow wave and REM sleep. During these stages of the sleep-wake cycle, coherence between CA1-CA2 was higher than CA1-CA3 and CA2-CA3 in the three animals evaluated, in three frequency bands: theta (6 to 12 Hz), slow gamma (30 to 50 Hz) and fast gamma (90 to 110 Hz) ipsilaterally. Coherence between contralateral fields was predominant in the theta band and almost zero in other frequencies. These results add to some previous published data showing that CA2 is distinct from the other subfields and that this small region of the Ammons horn may exert important roles in modulating activity in the other hippocampal fields and parahippocampal regions during memory and pathologies such as epilepsy

Le somnambulisme est un trouble du sommeil fréquent qui appartient à la famille des parasomnies NREM. Malgré des décennies de recherche, sa pathophysiologie reste peu comprise. Les études de familles et les études de jumeaux démontrent qu’une forte composante héréditaire est en jeu. Toutefois, très peu d’études moléculaires ont été menées afin d’identifier des gènes impliqués et il n’y a toujours pas de consensus quant au mode de transmission dans les familles. Cet ouvrage contient deux études distinctes qui tenteront de répondre à ces deux problèmes. L’objectif de la première étude était de déterminer si des variants génétiques dans le gène Adénosine désaminase (ADA) étaient enrichis dans la population somnambule en comparaison avec les dormeurs sains. Le gène entier a été séquencé chez 251 patients somnambules provenant de Montréal et de Montpellier ainsi que chez 94 sujets contrôles sans histoire personnelle ni familiale de somnambulisme. Aucun variant génétique n’était enrichi chez les patients somnambules en comparaison avec les dormeurs sains et les bases de données génétiques publiques. Dans la deuxième étude, le premier objectif était de déterminer le mode de transmission du somnambulisme chez 20 familles canadiennes-françaises. Le deuxième objectif était de mesurer le risque récurrent ainsi que le risque relatif pour la fratrie et les enfants des patients index. Dans notre cohorte, le somnambulisme se transmettait principalement selon un mode autosomal dominant à pénétrance réduite. Les risques récurrents pour les apparentés de premier degré étaient : à vie 0,48 à 0,56, durant l’enfance 0,43 à 0,56 et à l’âge adulte 0,14 à 0,35. Les risques relatifs pour les apparentés de premier degré étaient : à vie 6,96 à 8,12, durant l’enfance 1,48 à 4,06 et à l’âge adulte 4,67 à 11,67 supérieurs à la population générale. D’autres études moléculaires comme le séquençage de l’exome et les études de liaison génétique dans les familles seront nécessaires afin d’identifier de nouveaux gènes candidats qui pourront agir à titre de biomarqueurs. Cela permettrait de faciliter le diagnostic et ultimement développer des approches thérapeutiques ciblées. / Sleepwalking is a common sleep disorder and it belongs to the family of NREM parasomnias. Despite decades of research, its pathophysiology remains poorly understood. Family and twin studies show that a strong hereditary component is involved. However, very few molecular studies have been conducted to identify the genes involved and there is still no consensus on the mode of transmission in families. This Master’s thesis contains two separate studies which will attempt to address these two problems. The aim of the first study was to determine whether genetic variants in the Adenosine Deaminase (ADA) gene were enriched in the sleepwalking population compared to healthy sleepers. The entire gene was sequenced in 251 sleepwalking patients from Montreal and Montpellier as well as in 94 control subjects with no personal or family history of sleepwalking. No genetic variants were enriched in sleepwalking patients compared to healthy sleepers and public genetic databases. In the second study, the first objective was to determine the mode of transmission of sleepwalking in 20 French-Canadian families. The second objective was to measure the recurrence risk as well as the relative risk for siblings and children of index patients. In our cohort, sleepwalking was transmitted mainly in an autosomal dominant mode with reduced penetrance. The recurrence risks for first-degree relatives were: lifetime 0.48 to 0.56, in childhood 0.43 to 0.56, and in adulthood 0.14 to 0.35. The relative risks for first-degree relatives were: lifetime 6.96 to 8.12, in childhood 1.48 to 4.06 and in adulthood 4.67 to 11.67 higher than the general population. Further molecular studies, such as exome sequencing, and genetic linkage studies in families will be needed in order to identify new candidate genes that can act as biomarkers. This would allow the development of an independent test for the diagnosis and ultimately have implications for targeted therapeutic approaches.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

No description available.

Slow-wave sleep plays an important role in consolidation of declarative memory. From electrophysiological point of view, this process is dependent on a common occurrence and mutual integration of neocortical slow oscillations (< 1 Hz), hippocampal sharp-wave ripples (150-250 Hz) and thalamo-cortical sleep spindles (10-15 Hz). Previous studies demonstrated that periodic acoustic stimulation by pink noise pulses applied at frequency of sleep slow oscillation during slow wave sleep leads to prolongation of slow wave sleep and to enhancement in declarative memory performance in normal sleepers. Our study investigated this kind of periodic acoustic stimulation in its relation to sleep architecture and declarative memory of people suffering from insomnia due to which there often comes to a reduction in slow wave sleep which positively correlates with worsening of declarative memory performance. Our aim was to investigate if this kind of comparatively non-invasive brain stimulation has a potential to increase a total length of slow wave sleep and enhance declarative memory performance in insomnia. Our study revealed acoustic stimulation neither improved declarative memory performance nor it increased total length of slow-wave sleep. No positive association was found between level of declarative memory...

This thesis provides a novel dynamic large-scale network perspective on brain activity of human sleep based on the analysis of unique human neuroimaging data. Specifically, I provide new information based on integrating spatial and temporal aspects of brain activity both in the transitions between and during wakefulness and various stages of non-rapid-eye movement (NREM) sleep. This is achieved through investigations of inter-regional interactions, functional connectivity (FC), between activity timecourses throughout the brain. Overall, the presented findings provide new important whole-brain insights for our current understanding of sleep, and potentially also of sleep disorders and consciousness in general. In Chapter 2 I present a robust global increase in similarity between the structural connectivity (SC) and the FC in slow-wave sleep (SWS) in almost all of the participants of two independent fMRI datasets. This could point to a decreased state repertoire and more rigid brain dynamics during SWS. Chapter 2 further identifies the changes in FC strengths between wakefulness and individual stages of NREM sleep across the whole-brain fMRI network. I report connectivity in posterior parts of the brain as particularly strong during wakefulness, while connections between temporal and frontal cortices are increased in strength during N1 and N2 sleep. SWS is characterised by a global drop in FC. In Chapter 3 I take advantage of rare MEG recordings of NREM sleep to show, for the first time, the feasibility of constructing source-space FC networks of sleep using power envelope correlations. The increased temporal information of MEG signals allows me to identify the specific frequencies underlying the FC differences identified in Chapter 2 with fMRI. The beta band (16 – 30 Hz) thus stands out as important for the strong posterior connectivity of wakefulness, while a range of frequency bands from delta (0.25 – 4 Hz) to sigma (13 – 16 Hz) all appear to contribute to N2-specific FC increases. Consistent with the fMRI results, slow-wave sleep shows the lowest level of FC. Interestingly, however, the MEG signals suggest a fronto-temporal network of high connectivity in the alpha band, possibly reflecting memory processes. In Chapter 4 I expand the within-frequency FC analysis of Chapter 3 to explore potential cross-frequency interactions in the MEG FC networks. It is shown that N2 sleep involves an abundance of frequency cross-talk, while SWS includes very little. A multi-layer network approach shows that the gamma band (30 – 48 Hz) is particularly integrated in wakefulness. Chapter 5 addresses the identified MEG FC findings from the perspective of traditional spectral sleep staging. By correlating temporal changes in spectral power at the sensor level to fluctuations in average FC, a specific type of transient events is found to underlie the strong N2-specific coupling in static FC values. Lastly, in Chapter 6 I make the leap out of the constraints of traditional low-resolution sleep staging, and extract dynamic states of FC from fMRI timecourses in a completely unsupervised fashion. This provides a novel representation of whole-brain states of sleep and the dynamics governing them. I argue that data-driven approaches like this are necessary to fully characterise the spatiotemporal principles underlying wakefulness and sleep in the human brain.

There is a noticeable difference in the debate regarding adolescents’ sleep patterns between the biological clock and society’s clock when we talk about adolescents. Sleep scientists or somnologists, are alarming as more evidence reach the surface that young people are not getting the recommended sleep that is required to perform academically well. Not only are there direct connections between sleep deficit and academic performance, but sleep deficit also takes a critical toll upon their physical and mental health. The problem is that adolescents’ circadian cycle is postponed with a few hours compared to children and adults. This results in a major sleep deficit when adolescents must adjust to societal rhythms and habits – a clock they are not programmed biologically to follow. Adolescents must attend to school in the early morning, when in reality their needs point to that school times in fact should start around 10:00. Society’s view has traditionally been that teenagers are lazy but in fact evidence does prove that it may not be the case. The following essay will therefore serve as an informative update to what has been stated by somnologists and raise awareness regarding adolescents and what happens when they are exposed to a chronic sleep deficit put on them by society.