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  • Sleep- and Wake-Like States in Small Networks In Vivo and In Vitro.

    27 November 2018

    Wakefulness and sleep are highly complex and heterogeneous processes, involving multiple neurotransmitter systems and a sophisticated interplay between global and local networks of neurons and non-neuronal cells. Macroscopic approaches applied at the level of the whole organism, view sleep as a global behaviour and allow for investigation into aspects such as the effects of insufficient or disrupted sleep on cognitive function, metabolism, thermoregulation and sensory processing. While significant progress has been achieved using such large-scale approaches, the inherent complexity of sleep-wake regulation has necessitated the development of methods which tackle specific aspects of sleep in isolation. One way this may be achieved is by investigating specific cellular or molecular phenomena in the whole organism in situ, either during spontaneous or induced sleep-wake states. This approach has greatly advanced our knowledge about the electrophysiology and pharmacology of ion channels, specific receptors, intracellular pathways and the small networks implicated in the control and regulation of the sleep-wake cycle. Importantly though, there are a variety of external and internal factors that influence global behavioural states which are difficult to control for using these approaches. For this reason, over the last few decades, ex vivo experimental models have become increasingly popular and have greatly advanced our understanding of many fundamental aspects of sleep, including the neuroanatomy and neurochemistry of sleep states, sleep regulation, the origin and dynamics of specific sleep oscillations, network homeostasis as well as the functional roles of sleep. This chapter will focus on the use of small neuronal networks as experimental models and will highlight the most significant and novel insights these approaches have provided.

  • An intervention to improve sleep for people living with dementia: Reflections on the development and co-production of DREAMS:START (Dementia RElAted Manual for Sleep: STrAtegies for RelaTives).

    27 November 2018

    Many people living with dementia experience sleep disturbances yet there are currently no known effective, safe and acceptable treatments. Working with those affected by dementia to co-produce interventions is increasingly promoted to ensure that approaches are fit for purpose and meet the specific needs of target groups. Our aim here is to outline and reflect upon the co-production of Dementia RElAted Manual for Sleep; STrAtegies for RelaTives (DREAMS:START), an intervention to improve sleep for people living with dementia. Our co-production team brought together experts in the development and testing of manualised interventions in dementia care and cognitive behavioural interventions for sleep disorders, with Alzheimer's Society research network volunteers (ASRNVs) whose lives had been affected by dementia. Here we present the process of intervention development. We worked with (ASRNVs) at each stage of the process bringing together 'experts by training' and 'experts by experience'. (ASRNVs)shared their experiences of sleep disturbances in dementia and how they had managed these difficulties, as well as suggestions for how to overcome barriers to putting the intervention into practice; making (DREAMS:START) more accessible and usable for those in need. In this paper we discuss both the benefits and challenges to this process and what we can learn for future work. Collaborating with 'experts by experience' caring for a relative with sleep difficulties helped us to develop a complex intervention in an accessible and engaging way which we have tested and found to be feasible and acceptable in a randomised controlled trial.

  • The suitability of actigraphy, diary data, and urinary melatonin profiles for quantitative assessment of sleep disturbances in schizophrenia: a case report.

    27 November 2018

    Sleep disruption is a commonly encountered clinical feature in schizophrenic patients, and one important concern is to determine the extent of this disruption under "real" life situations. Simultaneous wrist actigraphy, diary records, and repeated urine collection for urinary 6-sulphatoxymelatonin (aMT6s) profiles are appropriate tools to assess circadian rhythms and sleep patterns in field studies. Their suitability for long-term recordings of schizophrenic patients living in the community has not been evaluated. In this case report, we document long-term simultaneous wrist actigraphy, light detection, repeated urine collection, and diary records as a suitable combination of non-invasive techniques to quantify and assess changes in sleep-wake cycles, light exposure, and melatonin profiles in a schizophrenic patient. The actigraph was well-tolerated by the patient, and compliance to diary records and 48 h urine collection was particularly good with assistance from family members. The data obtained by these techniques are illustrated, and the results reveal remarkable abnormal patterns of rest-activity patterns, light exposure, and melatonin production. We observed various rest-activity patterns, including phase-shifts, highly delayed sleep on- and offsets, and irregular rest-activity phases. The period of the rest-activity rhythm, light-dark cycle, and melatonin rhythm was longer than 24 h. These circadian abnormalities may reinforce the altered sleep patterns and the problems of cognitive function and social engagement associated with schizophrenic.

  • Non-rod, non-cone photoreception in rodents and teleost fish.

    27 November 2018

    Until recently, all ocular photoreception was attributed to the rods and cones of the retina. However, studies on mice lacking rod and cone photoreceptors (rd/rd cl), has shown that these mice can still use their eyes to detect light to regulate their circadian rhythms, suppress pineal melatonin, modify locomotor activity and modulate pupil size. In addition, action spectra for some of these responses have characterized a novel opsin/vitamin A-based photopigment with a lambda(max) approximately 480 nm. Electrophysiological studies have shown that a subset of retinal ganglion cells are intrinsically photosensitive, and melanopsin has been proposed as the photopigment mediating these responses to light. In contrast to mammals, an inner retinal photopigment gene has been identified in teleost fish. Vertebrate ancient (VA) opsin forms a photopigment with a lambda(max) between 460-500 nm, and is expressed in a sub-set of retinal horizontal cells, and cells in the amacrine and ganglion cell layers. Electrophysiological analysis suggests that VA opsin horizontal cells are intrinsically photosensitive and encode irradiance information. In contrast to mammals, however, the function of these novel ocular photoreceptors remains unknown. We compare non-rod, non-cone ocular photoreceptors in mammals and fish, and examine the criteria used to place candidate photopigment molecules into a functional context.

  • Responses to light after retinal degeneration.

    27 November 2018

    Transgenic rodless mice were given 1-h pulses of light of varying brightness at times of the night when they were normally active. The rodless mice showed decreases in locomotor activity during light pulses brighter than 2 lux; these decreases were significantly greater than those in wildtypes (ANOVA, P < 0.01). However, with very dim light, rodless mice showed no changes in activity, whereas wildtype mice actually increased their activity. It is suggested that irradiance detection could be enhanced by absence of image-forming vision. Enhanced inhibition of activity around twilight may be adaptive for mice in some circumstances and so help maintain genes for retinal degeneration in natural populations.