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Sensory input to the master mammalian circadian clock, the suprachiasmatic nucleus (SCN), is vital in allowing animals to optimize physiology and behaviour alongside daily changes in the environment. Retinal inputs encoding changes in external illumination provide the principle source of such information. The SCN also receives input from other retinorecipient brain regions, primarily via the geniculohypothalamic tract (GHT), although the contribution of these indirect projections to circadian photoreception is currently poorly understood. To address this deficit, in the present study, we established an in vitro mouse brain slice preparation that retains connectivity across the extended circadian system. Using multi-electrode recordings, we first confirm that this preparation retains intact optic projections to the SCN, thalamus and pretectum and a functional GHT. We next show that optogenetic activation of GHT neurons selectively suppresses SCN responses to retinal input, and also that this effect exhibits a pronounced day/night variation and involves a GABAergic mechanism. This inhibitory action was not associated with overt circadian rhythmicity in GHT output, indicating modulation at the SCN level. Finally, we use in vivo electrophysiological recordings alongside pharmacological inactivation or optogenetic excitation to show that GHT signalling actively modulates specific features of the SCN light response, indicating that GHT cells are primarily activated by crossed retinal projections. Taken together, our data establish a new model for studying network communication in the extended circadian system and provide novel insight into the roles of GHT-signalling, revealing a mechanism by which thalamic activity can help gate retinal input to the SCN according to time of day.

The development of educational multimedia since 1994 has been characterised by a rapid expansion of new technologies. In the context of an exciting and controversial exploration of\ud techniques, research into how children used computers in the classroom had been limited. The thesis therefore included a wide-ranging study into factors informing a deeper understanding of the way 5 to7-year-old school children use interactive computer programs. The thesis originated in contextual studies undertaken by the researcher in classrooms. The contextual research raised issues that are not the common ground of educational multimedia practitioners. These issues were explored in depth in the literature review. The thesis tested the potential improvements in interface design - an interactive educational CD-ROM using audio and visual resources from a BBC School Radio music series. The focus was not the music content or the teaching of the subject. The results of testing the research tool that used observation of groups of three children, interviews with individual children and teachers were summarised and improvements identified. The aim was to seek answers to the question 'How can the quality of computer interface interaction be improved?' Improvements were considered by\ud enhancing the quality of interaction through greater depth of engagement by using the computer mouse to move icons on the computer screen. \ud \ud In the process of contextual research the following issues were raised: the need for teachers to have a method of mediating the content of educational CD-ROMs, the physiological demands made on children in terms of eye search; the difficulties they encountered using navigation\ud metaphors; and the potential of pseudo 3-D perspective interfaces. The research re-evaluates the relationship between children and computers in the familiar context of groups of three children using computers in the primary classroom, and resulted in a coherent set of suggestions for a more effective holistic paradigm for the design of multimedia programs that\ud takes into account practical realities in classroom environments.\ud ..

The epithalamic lateral habenula (LHb) is implicated as part of the mammalian brain's circadian system. Anatomical evidence suggests that the LHb receives extrinsic circadian timing cues from retinal ganglion cells and the master clock in the suprachiasmatic nuclei (SCN). Intriguingly, some LHb neurones contain the molecular circadian clock, but it is unclear if and how intrinsic and extrinsic circadian processes influence neuronal activity in the mouse LHb. Here, using an in vitro brain slice preparation isolating the LHb from the SCN, we show through whole-cell patch-clamp recordings that LHb neurones exhibit heterogeneity in their resting state, but the majority spontaneously fire action potentials (APs). Discharge rate of APs varied from low firing in the early day to higher firing later in the day and was absent in LHb brain slices prepared from Cry1−/−Cry2−/− mice that lack a functional molecular clock. Low amplitude circadian oscillations in the molecular circadian clock were also monitored in LHb brain slices, but were absent in Cry1−/−Cry2−/− LHb brain tissue. A putative neurochemical output signal of the SCN, prokineticin 2 (PK2), inhibited some LHb neurones by elevating the frequency of GABA release in the LHb. Using multi-electrode recordings in vivo, we found that LHb neurones sluggishly respond to retinal illumination, suggesting that they receive such information through polysynaptic processes. In summary, our results show for the first time that intrinsic circadian signals are important for regulating LHb neuronal state, while the SCN-derived signal PK2 is less influential. Moreover, we demonstrate that mouse LHb neurones have access to and can respond to visual input, but such signals are unlikely to be directly communicated to the LHb. Broadly, these findings raise the possibility that intrinsic circadian signals are likely to be influential in shaping LHb contributions to cognition and emotionality.

A key task for the visual system is to combine spatially overlapping representations of the environment, viewed by either eye, into a coherent image. In cats and primates, this is accomplished in the cortex [1], with retinal outputs maintained as separate monocular maps en route through the lateral geniculate nucleus (LGN). While this arrangement is also believed to apply to rodents [2, 3], this has not been functionally confirmed. Accordingly, here we used multielectrode recordings to survey eye-specific visual responses across the mouse LGN. Surprisingly, while we find that regions of space visible to both eyes do indeed form part of a monocular representation of the contralateral visual field, we find no evidence for a corresponding ipsilateral representation. Instead, we find many cells that can be driven via either eye. These inputs combine to enhance the detection of weak stimuli, forming a binocular representation of frontal visual space. This extensive thalamic integration marks a fundamental distinction in mechanisms of binocular processing between mice and other mammals.