Clock neurons gate memory extinction in Drosophila

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Sleep wakefulness cycle

Abstract

48 right‐handed subjects performed verbal and spatial hemifield tachistoscopic tasks, half of them in spring and the other half in autumn. Significant differences were detected showing increased right visual field (left hemisphere) advantage in spring and increased left visual field (right hemisphere) advantage in autumn. Results may help to explain the reported seasonal propensity towards elevated mood in spring and towards depressed mood in autumn as related to the relative role of both hemispheres.     

Sleep and biological rhythms of Drosophila

Sleep and Biological Rhythms -     

The UPR and the Anti-oxidant Response: Relevance to Sleep and Sleep Loss

Oxidative stress has been linked to various physiological and pathological processes such as aging and neurological disorders. Recent evidence has now implicated a role for oxidative stress in sleep and sleep loss. Studies suggest that wakefulness results in an oxidative burden and sleep provides a protective mechanism against these harmful effects. Prolonged wakefulness/sleep deprivation activates an adaptive stress pathway termed the unfolded protein response (UPR), which temporarily guards against the deleterious consequences of reactive oxygen species. The UPR affects the function of the endoplasmic reticulum, which is the site for integral and secretory membrane processing and folding. Several downstream effectors of the UPR operate in an antioxidant capacity to reduce the load of these toxic species; a process that may be important in delaying the progression of neurodegenerative diseases. This review will highlight the molecular components of the UPR that ameliorate the accumulation of oxidative stress and may therefore provide potential therapeutic targets.     

A Paradoxical Kind of Sleep in Drosophila melanogaster

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Coupling Neuropeptide Levels to Structural Plasticity in Drosophila Clock Neurons

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Exaggerated Nighttime Sleep and Defective Sleep Homeostasis in a Drosophila Knock-In Model of Human Epilepsy

Despite an established link between epilepsy and sleep behavior, it remains unclear how specific epileptogenic mutations affect sleep and subsequently influence seizure susceptibility. Recently, Sun et al. (2012) created a fly knock-in model of human generalized epilepsy with febrile seizures plus (GEFS+), a wide-spectrum disorder characterized by fever-associated seizing in childhood and lifelong affliction. GEFS+ flies carry a disease-causing mutation in their voltage-gated sodium channel (VGSC) gene and display semidominant heat-induced seizing, likely due to reduced GABAergic inhibitory activity at high temperature. Here, we show that at room temperature the GEFS+ mutation dominantly modifies sleep, with mutants exhibiting rapid sleep onset at dusk and increased nighttime sleep as compared to controls. These characteristics of GEFS+ sleep were observed regardless of sex, mating status, and genetic background. GEFS+ mutant sleep phenotypes were more resistant to pharmacologic reduction of GABA transmission by carbamazepine (CBZ) than controls, and were mitigated by reducing GABA_A receptor expression specifically in wake-promoting pigment dispersing factor (PDF) neurons. These findings are consistent with increased GABAergic transmission to PDF neurons being mainly responsible for the enhanced nighttime sleep of GEFS+ mutants. Additionally, analyses under other light conditions suggested that the GEFS+ mutation led to reduced buffering of behavioral responses to light on and off stimuli, which contributed to characteristic GEFS+ sleep phenotypes. We further found that GEFS+ mutants had normal circadian rhythms in free-running dark conditions. Interestingly, the mutants lacked a homeostatic rebound following mechanical sleep deprivation, and whereas deprivation treatment increased heat-induced seizure susceptibility in control flies, it unexpectedly reduced seizure activity in GEFS+ mutants. Our study has revealed the sleep architecture of a Drosophila VGSC mutant that harbors a human GEFS+ mutation, and provided unique insight into the relationship between sleep and epilepsy.     

Limit cycle model for brain waves

The extraordinary high sensitivity of certain biological systems to weak electromagnetic signals motivated Fröhlich to establish his brain wave model. Although the basic assumptions of such a model are still highly speculative, it seems worth while to investigate the quantitative dynamics of it. In this model coherent excitations in the 10¹¹ Hz region in combination with a collective enzyme-substrate reaction create and stabilize a limit cycle oscillation. In the present paper the existence of the limit cycle and its collapse due to external stimulation is studied. The bifurcation of this periodically oscillating resting state is analysed and the stability of additional steady states is proven. Approximations are discussed and a correspondence between the limit cycle model and nerve impulse generating models is established.     

Sleep Loss and Performance of Anaesthesia Trainees and Specialists

Fatigue risk associated with work schedules of hospital doctors is coming under increasing scrutiny, with much of the research and regulatory focus on trainees. However, provision of 24 h services involves both trainees and specialists, who have different but interdependent work patterns. This study examined work patterns, sleep (actigraphy, diaries) and performance (psychomotor vigilance task pre‐ and post‐duty) of 28 anaesthesia trainees and 20 specialists across a two‐week work cycle in two urban public hospitals. Trainees at one hospital worked back‐to‐back 12 h shifts, while the others usually worked 9 h day shifts but periodically worked a 14 h day (08:00–22:00 h) to maintain cover until arrival of the night shift (10 h). On 11% of day shifts and 23% of night shifts, trainees were working with ≥2 h of acute sleep loss. However, average sleep loss was not greater on night shifts, possibly because workload at night in one hospital often permitted some sleep. Post‐night shift performance was worse than post‐day shift performance for the median (t₍₁₃₁₎=3.57, p<0.001) and slowest 10% of reaction times (t₍₁₃₄₎=2.91, p<0.01). At the end of night shifts, poorer performance was associated with longer shift length, longer time since waking, greater acute sleep loss, and more total work in the past 24 h. Specialists at both hospitals had scheduled clinical duties during the day and were periodically scheduled on call to cover after‐hours services. On 8% of day shifts and 14% of day+call schedules, specialists were working with ≥2 h of acute sleep loss. They averaged 0.6 h less sleep when working day shifts (t_(23.5)=2.66, p=0.014) and 0.8 h less sleep when working day shifts+call schedules (t_(26.3)=2.65, p=0.013) than on days off. Post‐duty reaction times slowed linearly across consecutive duty days (median reaction time, t₍₁₃₁₎=?3.38, p<0.001; slowest 10%, t₍₁₆₀₎=?3.33, p<0.01; fastest 10%, t₍₁₃₈₎=?2.67, p<0.01). Poorer post‐duty performance was associated with greater acute sleep loss and longer time since waking, but better performance was associated with longer day shifts, consistent with circadian improvement in psychomotor performance across the waking day. This appears to be the first study to document sleep loss among specialist anaesthetists. Consistent with observations from experimental studies, the sleep loss of specialists across 12 consecutive working days was associated with a progressive decline in post‐duty PVT performance. However, this decline occurred with much less sleep restriction (< 1 h per day) than in laboratory studies, suggesting an exacerbating effect of extended wakefulness and/or cumulative fatigue associated with work demands. For both trainees and specialists, robust circadian variation in PVT performance was evident in this complex work setting, despite the potential confounds of variable shift durations and workloads. The relationship between PVT performance of an individual and the safe administration of anaesthesia in the operating theater is unknown. Nevertheless, the findings reinforce that any schedule changes to reduce work‐related fatigue need to consider circadian performance variation and the potential transfer of workload and fatigue risk between trainees and specialists.     

Presynaptic Active Zone Plasticity Encodes Sleep Need in Drosophila

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