Rapid eye movements during sleep in mice: High trait-like stability qualifies rapid eye movement density for characterization of phenotypic variation in sleep patterns of rodents

<p>Abstract</p> <p>Background</p> <p>In humans, rapid eye movements (REM) density during REM sleep plays a prominent role in psychiatric diseases. Especially in depression, an increased REM density is a vulnerability marker for depression. In clinical practice and research measurement of REM density is highly standardized. In basic animal research, almost no tools are available to obtain and systematically evaluate eye movement data, although, this would create increased comparability between human and animal sleep studies.</p> <p>Methods</p> <p>We obtained standardized electroencephalographic (EEG), electromyographic (EMG) and electrooculographic (EOG) signals from freely behaving mice. EOG electrodes were bilaterally and chronically implanted with placement of the electrodes directly between the musculus rectus superior and musculus rectus lateralis. After recovery, EEG, EMG and EOG signals were obtained for four days. Subsequent to the implantation process, we developed and validated an Eye Movement scoring in Mice Algorithm (EMMA) to detect REM as singularities of the EOG signal, based on wavelet methodology.</p> <p>Results</p> <p>The distribution of wakefulness, non-REM (NREM) sleep and rapid eye movement (REM) sleep was typical of nocturnal rodents with small amounts of wakefulness and large amounts of NREM sleep during the light period and reversed proportions during the dark period. REM sleep was distributed correspondingly. REM density was significantly higher during REM sleep than NREM sleep. REM bursts were detected more often at the end of the dark period than the beginning of the light period. During REM sleep REM density showed an ultradian course, and during NREM sleep REM density peaked at the beginning of the dark period. Concerning individual eye movements, REM duration was longer and amplitude was lower during REM sleep than NREM sleep. The majority of single REM and REM bursts were associated with micro-arousals during NREM sleep, but not during REM sleep.</p> <p>Conclusions</p> <p>Sleep-stage specific distributions of REM in mice correspond to human REM density during sleep. REM density, now also assessable in animal models through our approach, is increased in humans after acute stress, during PTSD and in depression. This relationship can now be exploited to match animal models more closely to clinical situations, especially in animal models of depression.</p

Restless legs syndrome: Over 50 years of European contribution.

Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterised by an urge to move the limbs with a circadian pattern (occurring in the evening/at night), more prominent at rest, and relieved with movements. RLS is one of the most prevalent sleep disorders, occurring in 5%-10% of the European population. Thomas Willis first described RLS clinical cases already in the 17th century, and Karl-Axel Ekbom described the disease as a modern clinical entity in the 20th century. Despite variable severity, RLS can markedly affect sleep (partly through the presence of periodic leg movements) and quality of life, with a relevant socio-economic impact. Thus, its recognition and treatment are essential. However, screening methods present limitations and should be improved. Moreover, available RLS treatment options albeit providing sustained relief to many patients are limited in number. Additionally, the development of augmentation with dopamine agonists represents a major treatment problem. A better understanding of RLS pathomechanisms can bring to light novel treatment possibilities. With emerging new avenues of research in pharmacology, imaging, genetics, and animal models of RLS, this is an interesting and constantly growing field of research. This review will update the reader on the current state of RLS clinical practice and research, with a special focus on the contribution of European researchers

Cortico-autonomic local arousals and heightened somatosensory arousability during NREMS of mice in neuropathic pain.

Frequent nightly arousals typical for sleep disorders cause daytime fatigue and present health risks. As such arousals are often short, partial, or occur locally within the brain, reliable characterization in rodent models of sleep disorders and in human patients is challenging. We found that the EEG spectral composition of non-rapid eye movement sleep (NREMS) in healthy mice shows an infraslow (~50 s) interval over which microarousals appear preferentially. NREMS could hence be vulnerable to abnormal arousals on this time scale. Chronic pain is well-known to disrupt sleep. In the spared nerve injury (SNI) mouse model of chronic neuropathic pain, we found more numerous local cortical arousals accompanied by heart rate increases in hindlimb primary somatosensory, but not in prelimbic, cortices, although sleep macroarchitecture appeared unaltered. Closed-loop mechanovibrational stimulation further revealed higher sensory arousability. Chronic pain thus preserved conventional sleep measures but resulted in elevated spontaneous and evoked arousability. We develop a novel moment-to-moment probing of NREMS vulnerability and propose that chronic pain-induced sleep complaints arise from perturbed arousability

Restless legs syndrome: diagnosis, treatment and pathophysiology

This cumulative dissertation presents four articles focussing on diagnosis, treatment and pathophysiology of the restless legs syndrome: 1) Fulda S, Beitinger ME, Reppermund S, Winkelmann J, Wetter TC. Short-term attention and verbal fluency is decreased in restless legs syndrome patients. Movement Disorders 2010; 25: 2641-2648. DOI 10.1002/mds.23353 2) Fulda S, Wetter TC. Where dopamine meets opioids: a meta-analysis of the placebo effect in restless legs syndrome treatment studies. Brain 2008; 131: 902-917. DOI 10.1093/brain/awm244 3) Fulda S, Stalla GK, Wetter TC. Prevalence of the restless legs syndrome in transsexual patients: the hormonal hypothesis revisited. Journal of Neurology 2007; 254: 1748-1749. DOI 10.1007/100415-007-0624-6 4) Winkelmann J, Schormaier B, Lichtner P, Ripke S, Xiong L, Jalilzadeh S, Fulda S, Pütz B, Eckstein G, Hauk S, Trenkwalder C, Zimprich A, Stiasny-Kolster K, Oertel W, Bachmann CG, Paulus W, Peglau I, Eisensehr I, Montplaisir J, Turecki G, Rouleau G, Gieger C, Illig T, Wichmann HE, Holsboer F, Müller-Myhsok B, Meitinger T. Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet 2007; 39(8): 1000-1006. DOI 10.1038/ng209

Characteristics and Determinants of Respiratory Event-Associated Leg Movements

Abstract Study Objectives To (1) replicate the recently described distribution of respiratory event-associated leg movements (rLMs) in participants with mild-to-moderate obstructive sleep apnea syndrome (OSAS), (2) explore global and local factors associated with the presence of rLMs, and (3) investigate differences related to OSAS severity and periodic leg movements during sleep (PLMS) status. Methods We randomly selected six groups of participants without restless legs syndrome (12-15 participants in each group), stratified by apnea-hypopnea index (AHI) severity (AHI 10-20, 20-30, and 30-40) and PLMS status (PLMS index 15 per hr) from the population-based HypnoLaus study that assessed full polysomnography at home in participants aged 40 to 80 years, randomly selected from the population register of the city of Lausanne, Switzerland. Results Our results confirmed the distribution of leg movement activity at the end of respiratory events (−2.0 to +10.25 s). Mixed effects logistic regression modeling rLM-probability showed that rLMs were more frequent in participants with high-PLMS, at the end of obstructive apneas (vs. hypopneas) and in the presence of arousals at the end of the events. In participants with high-PLMS, rLM-probability decreased with time of night and was more reduced during REM sleep (vs. NREM sleep), whereas the duration of the respiratory event had a significant effect only in participants with low-PLMS. Conclusions We confirm the previously reported distribution of rLMs in participants with mild-to-moderate OSAS and our results suggest that rLMs are sensitive to both sleep-related and respiratory-related factors in a complex interaction with the PLMS status

Western Star, 1907-09-04

The Western Star began publication on Newfoundland's west coast on 4 April 1900, appearing weekly with brief semiweekly periods up to 1952, when it became a daily. As of 17 April 2019 it continues as a free weekly community paper