Early light environment has been shown to alter locomotor activity behaviour in adult rats and mice when exposed to constant light (LL), constant darkness (DD) or 12:12 hour light-dark cycles (LD). In particular, exposure to LL during lactation results in an increased ability to cope with exposure to LL as adults, implying that the ability to interpret light information is altered depending on early light environment. Therefore, the aim of this project was to explore how early light environment affects the photic response of the circadian system. The retina forms the first component of the photic response of the circadian system. We wanted to know whether being raised in DD, LD or LL would alter retinal function or structure in adult CD1 (albino) and C57BL/6J (pigmented) mice. We found that in CD1 mice, being raised in LL caused significant retinal damage and a significant reduction in retinal function. In C57BL/6J mice, we saw no such changes, implying that any changes that we see in behaviour would be due to alterations further downstream, such as the suprachiasmatic nucleus (SCN), site of the master circadian clock in the mammalian brain. We next exposed C57BL/6J mice to LL and found that mice raised in DD had significantly longer taus than mice raised in LL, implying that mice raised in DD are more sensitive to light than mice raised in LL.Previous work has shown that early light environment alters neuropeptide and astrocyte expression in the SCN of C57BL/6J mice. Furthermore, early light environment produces opposite behavioural responses in CD1 and C57BL/6J mice when exposed to LD as adults. We therefore examined how neuropeptide and astrocyte expression would be affected by early light environment in CD1 mice and whether this would reflect the differential behavioural response. We found that neuropeptide and astrocyte expression in the SCN seemed to be affected by the level of retinal damage and/or the type and intensity of the light source used. This sensitivity to lighting environment makes CD1 mice unsuitable for further studies on the photic response of the circadian system. Pigmented mice were used for the remainder of this project. The photic response of the circadian system can be quantified using a phase response curve (PRC) which measures behavioural responses to light pulses administered at different times of day. We measured the effect of a light pulse on the delay and advance portion of the PRC and found no differences due to early light environment, implying that the phasic effect of light is not altered by early light environment. Light pulses administered during the subjective night result in the upregulation of SCN intracellular photic signalling pathways. After a light pulse given during the early subjective night, we found no differences in the upregulation of different components of the photic signalling pathway due to early light environment indicating early light environment does not seem to affect the initial photic signalling pathway in the SCN.Finally, recent advances in molecular biology allow for real-time monitoring of clock gene expression in vitro. Using mPer2::luc mice, we monitored in vitro PER2::LUC expression to determine the effects of early light environment on clock gene expression. In the SCN, we found that the amplitude of PER2::LUC expression was significantly reduced in mice raised in DD compared to mice raised in LD and LL. These results suggest that early light environment affects the coupling strength between SCN neurons and this may be the mechanism mediating the changes in behaviour we have measured. In peripheral tissue, we found altered PER2::LUC expression due to early light environment in the heart, lung and spleen, implying that early light environment not only alters behaviour but may also affect heart and lung function and the immune system.

The suprachiasmatic nucleus receives dense serotonergic projections from the raphe nuclei and this input has been implicated in the modulation of circadian rhythms. This input appears to have many functions including the transmission of non-photic information during the day and the modulation of photic information at night. However, it has emerged that this input may also be involved in the transmission of light information with activation of 5-HT2C receptors at night having a photo-mimetic effect. The studies described in this thesis aim to clarify the role of 5-HT2C receptors in the control of circadian rhythms in the rat model and compare their actions to light. The acute effects of 5-HT2C receptor agonist administration on clock gene expression were investigated in the rat SCN. Systemic administration of the 5-HT2A/2C agonist DOI to rats during early night induced c-fos, Per1 and Per2 expression in a manner similar to light. This response was time of day dependent with maximal induction occurring in the early night, and no response during the day. The role of 5-HT2C receptors in this response was confirmed with the use of the selective 5-HT2C receptor agonist RO-60 0175. The effect of 5-HT2C receptor activation on the phase of expression of various circadian rhythms including temperature, melatonin and clock gene expression in the SCN and periphery was examined. Both DOI administration and light exposure at night phase delayed rhythms of melatonin and temperature. Similarly, the selective 5-HT2C receptor agonist RO-60 0175 phase delayed rhythms of 6-sulphatoxymelatonin, a response which was antagonised by the 5-HT2C receptor antagonist SB-242084. The expression of functional and clock genes within the pineal was also phase delayed following both light and 5-HT2C receptor agonist administration. However, the phase of expression of clock genes within the SCN or liver did not shift in response to either a single nocturnal light pulse or agonist administration. To investigate the site of action of 5-HT2C receptor agonists, rat SCN explants were maintained in culture allowing exposure of agonists to denervated tissue. The acute effect of DOI administration at various circadian times on c-fos and Per1 expression was assessed. 5-HT2C receptor activation significantly increased Per1 expression when administered during early subjective night, but had no effect during either subjective day or late subjective night, similar to that observed in vivo. Finally, the suitability of immortalised rat SCN cells for investigation of the intracellular actions of 5-HT2C receptors in the circadian system was assessed. Using RT-PCR the expression of various serotonin receptors in the SCN2.2 cell line was compared with that observed in punches of adult rat SCN. The mRNA for 5-HT1B and 5-HT2A receptor was expressed in both the SCN2.2 cell line and the adult rat SCN. However, 5-HT2C receptor mRNA along with 5-HT3 receptor, 5-HT5A receptor and 5-HT7 receptor mRNA was expressed in the adult rat SCN tissue but not the SCN2.2 cells. These significant differences in serotonin receptor expression limit the usefulness of this cell line for further investigation. Together these experiments further implicate 5-HT2C receptors in the control of circadian rhythms. The role of these receptors appears limited to early night, with activation showing photo-mimetic responses. Furthermore, the location of action appears to be post-synaptic within the SCN, altering the core clock genes, which in turn phase delay various circadian rhythms. / Thesis(Ph.D.)-- School of Paediatrics and Reproductive Health, 2008

Research has showed that different light scenarios have a profound effect on hospitalized bipolar patients. Different light situations decrease the hospital stay for patients during both manic and depressive episodes. Nevertheless, a field study carried out during this thesis work of two arbitrary patient rooms in Swedish behavioral health clinics showed no incorporation of this knowledge in the light design of the rooms. Both patient rooms had insufficient light levels both in terms of circadian recommendations and perceived brightness. Hence this thesis suggests an improved light design for patient rooms housing bipolar patients. The basis of the improved design is to incorporate a dynamic, circadian lighting that varies depending on the patient's need and diagnosed episode.

Syftet har varit att undersöka hur olika interiöra miljöer kan återges med ELF-metoden (Environmental Light Field Method) och om resultaten skiljt sig åt i olika miljöer. Studien har genomförts som ett experiment på Jönköpings Tekniska Högskola och insamling av data har skett i lektionssalar, entré, bibliotek och utomhus genom en kvantitativ metod. Insamlade data genom ELF-metoden består av foton, diagram och mätresultat. ELF-resultaten har jämförts med rummens uppmätta belysningsstyrkor, spektralfördelningar och utredarnas upplevelse av rummen som presenterats genom skisser. Resultatet visar att ELF-metoden fungerar som en kombination av de andra mätmetoderna. Styrkan är att resultatet ger en samlad bild av miljön med hänsyn till ytfärger, intensitet och dagsljusinsläpp men dess nackdelar är att det idag är initialt tidskrävande samt att det endast går att utvärdera befintliga miljöer. Slutsatsen är att metoden i framtiden kan komma att bli lämplig för utvärdering av belysning och dagsljus i interiöra miljöer, när metoden för insamling och hantering av data har utvecklats och effektiviserats. / The purpose has been to investigate how different interior environments can be reproduced with the ELF method (Environmental Light Field Method) and whether the results differ in different environments. The study was conducted as an experiment at Jönköping University and data collection was done in classrooms, entrances, libraries and outdoors through a quantitative method. Collected data consists of photos, diagrams and measurement results. The ELF-results have been compared with the illuminance in the rooms, the spectral power distribution and the investigators experienced the room which is presented with sketches. The results show that the ELF method works as a combination of other measurement methods. The strength is that the result gives an overall picture of the environment regarding to surface colors, intensity and daylight input, but its disadvantages are that today it is initially time-consuming and that it is only possible to evaluate existing environments. The conclusion is that the method in the future may be suitable for evaluating lighting and daylight in interior environments when the method for collecting and processing data has been developed and streamlined.