The suprachiasmatic nucleus (SCN) is a complex structure dependent upon multiple mechanisms to ensure rhythmic electrical activity that varies between day and night, to determine circadian adaptation and behaviours. SCN neurons are exposed to glutamate from multiple sources including from the retino-hypothalamic tract and from astrocytes. However, the mechanism preventing inappropriate post-synaptic glutamatergic effects is unexplored and unknown. Unexpectedly we discovered that TRESK, a calcium regulated two-pore potassium channel, plays a crucial role in this system. We propose that glutamate activates TRESK through NMDA and AMPA mediated calcium influx and calcineurin activation to then oppose further membrane depolarisation and rising intracellular calcium. Hence, in the absence of TRESK, glutamatergic activity is unregulated leading to membrane depolarisation, increased nocturnal SCN firing, inverted basal calcium levels and impaired sensitivity in light induced phase delays. Our data reveals TRESK plays an essential part in SCN regulatory mechanisms and light induced adaptive behaviours.

The earth's rotation around its very own axis generates the phenomenon that we refer to as our day and night. This change in environmental lighting has been an essential component of life; where throughout the evolutionary chain, organisms have used this signal as a timing cue to which they regulate/ synchronise their sleep-wake activity. It is this entrainment of both phy- siological processes and behavioural traits that define and, in some aspects, govern an individual's life style through circadian linked routines. Mammals, are no exception to this rule, often being referred to as 'creatures of habit'. From inception through to old age humans tend to gravitate to structured and defined periodic sleep- wake patterns; an uncanny system innately programmed into every individual, contributing to good health and wellbeing. However, the caveat lies within the aging process itself. Aging of the physio- logical components that govern and maintain circadian rhythms in mammals result in disruption to the clock leading to problems in sleep, cognition and social function, to name but a few. Little is known regarding the underlying mechanisms driving such changes; thus, it is imperative that we understand the natural biological aging process so to develop therapies and treatments that improve the quality of life in our, ever growing, aging population.

In this study, polymeric microneedle patches were fabricated by stereolithography, a 3D printing technique, for the transdermal delivery of insulin. A biocompatible resin was photopolymerized to build pyramid and cone microneedle designs followed by inkjet print coating of insulin formulations., trehalose and xylitol were used as drug carriers with the aim to preserve insulin integrity and stability but also facilitate rapid release rates. Circular dichroism and Raman analysis demonstrated that all carriers maintained the native form of insulin with xylitol presenting the best performance. Franz cell release studies were used for in vitro determination of insulin release rates in porcine skin. Insulin was released rapidly within 30 min irrespectively of the microneedle design. 3D printing was proved an effective technology for the fabrication of biocompatible and scalable microneedle patches.

Robust physiological circadian rhythms form an integral part of wellbeing. The aging process has been found to negatively impact systems that drive circadian physiology, typically manifesting as symptoms associated with abnormal/ disrupted sleeping patterns. Here, we investigated the age-related decline in light-driven circadian entrainment in male C57BL/6J mice. We compared light-driven resetting of circadian behavioural activity in young (1-2 months) and old (14-18 months) mice and explored alterations in the glutamatergic pathway at the level of the circadian pacemaker, the suprachiasmatic nucleus (SCN). Aged animals showed a significant reduction in sensitivity to behavioural phase-resetting by light. We show that this change was through alterations in NMDA signalling at the SCN, where NMDA, a glutamatergic agonist, was less potent in inducing clock resetting. Finally, we show that this shift in NMDA sensitivity was through the reduced SCN expression of this receptor's NR2B subunit. Only in young animals did an NR2B antagonist attenuate behavioural resetting. These results can help target treatments that aim to improve both physiological and behavioural circadian entrainment in aged populations.

We report on the use of a single supercontinuum (SC) source for multimodal imaging. The 2-octave bandwidth (475-2300 nm) makes the SC source suitable for optical coherence tomography (OCT) as well as for multispectral photoacoustic microscopy (MPAM). The IR band centered at 1310 nm is chosen for OCT to penetrate deeper into tissue with 8 mW average power on the sample. The 500-840 nm band is used for MPAM. The source has the ability to select the central wavelength as well as the spectral bandwidth. An energy of more than 35 nJ within a less than 50 nm bandwidth is achieved on the sample for wavelengths longer than 500 nm. In the present paper, we demonstrate the capabilities of such a multimodality imaging instrument based on a single optical source. In-vitro mouse ear B-scan images are presented.