The Circadian Clock Gene Period1 Connects the Molecular Clock to Neural Activity in the Suprachiasmatic Nucleus.

The neural activity patterns of suprachiasmatic nucleus (SCN) neurons are dynamically regulated throughout the circadian cycle with highest levels of spontaneous action potentials during the day. These rhythms in electrical activity are critical for the function of the circadian timing system and yet the mechanisms by which the molecular clockwork drives changes in the membrane are not well understood. In this study, we sought to examine how the clock gene Period1 (Per1) regulates the electrical activity in the mouse SCN by transiently and selectively decreasing levels of PER1 through use of an antisense oligodeoxynucleotide. We found that this treatment effectively reduced SCN neural activity. Direct current injection to restore the normal membrane potential partially, but not completely, returned firing rate to normal levels. The antisense treatment also reduced baseline [Ca(2+)]i levels as measured by Fura2 imaging technique. Whole cell patch clamp recording techniques were used to examine which specific potassium currents were altered by the treatment. These recordings revealed that the large conductance [Ca(2+)]i-activated potassium currents were reduced in antisense-treated neurons and that blocking this current mimicked the effects of the anti-sense on SCN firing rate. These results indicate that the circadian clock gene Per1 alters firing rate in SCN neurons and raise the possibility that the large conductance [Ca(2+)]i-activated channel is one of the targets

From Transaction to Interaction: Socio-materiality, Reliability and Transparency in an Age of Unbound Documents

Social media applications, such as Facebook, have been described as “documents without borders”. (Skare & Lund, 2014). In an Australian Government context these documents (which may also be records) exist outside the boundaries of the organisation to which they relate, and which created them. Unlike other documents in an organisational setting, they are “unbound” from the usual organisational processes of creation, management and control but still subject to relevant legislative and recordkeeping obligations (Hesling, 2014). This paper explores initial themes from the first case study of a larger doctoral study into the perceptions of records in Australian Government agencies. Among these themes are that organisational processes and the socio-material nature of social media may affect how users construct their concepts around records and the transparency and the reliability of records in an age of “unbounded documents”

Time-Restricted Feeding Improves Circadian Dysfunction as well as Motor Symptoms in the Q175 Mouse Model of Huntington's Disease.

Huntington's disease (HD) patients suffer from a progressive neurodegeneration that results in cognitive, psychiatric, cardiovascular, and motor dysfunction. Disturbances in sleep/wake cycles are common among HD patients with reports of delayed sleep onset, frequent bedtime awakenings, and fatigue during the day. The heterozygous Q175 mouse model of HD has been shown to phenocopy many HD core symptoms including circadian dysfunctions. Because circadian dysfunction manifests early in the disease in both patients and mouse models, we sought to determine if early intervention that improve circadian rhythmicity can benefit HD and delay disease progression. We determined the effects of time-restricted feeding (TRF) on the Q175 mouse model. At six months of age, the animals were divided into two groups: ad libitum (ad lib) and TRF. The TRF-treated Q175 mice were exposed to a 6-h feeding/18-h fasting regimen that was designed to be aligned with the middle of the time when mice are normally active. After three months of treatment (when mice reached the early disease stage), the TRF-treated Q175 mice showed improvements in their locomotor activity rhythm and sleep awakening time. Furthermore, we found improved heart rate variability (HRV), suggesting that their autonomic nervous system dysfunction was improved. Importantly, treated Q175 mice exhibited improved motor performance compared to untreated Q175 controls, and the motor improvements were correlated with improved circadian output. Finally, we found that the expression of several HD-relevant markers was restored to WT levels in the striatum of the treated mice using NanoString gene expression assays

Records are practices, not artefacts: an exploration of recordkeeping in the Australian Government in the age of digital transition and digital continuity

University of Technology Sydney. Faculty of Arts and Social Sciences.Good record keeping is of critical importance to organisations, governments and societies at large, however the language of records management with its inflexible and dominant view of managing records as artefacts - the passive and objective by-products of business activity - tends to be the only lens through which the documentary reality of organizational life in the recordkeeping disciplines is examined. A more user-centric and holistic view is needed to produce better recordkeeping outcomes in organisations. This study applied a practice theoretical approach to explore the perspectives about records held by various professions employed across four different Australian Government agencies. The study also explored the influences of organizational culture and professional background on these perceptions. Using comparable sites, semi-structured interviews and documentary analysis were carried out. This approach to the study is significant as it is the first study to use a practice theoretical approach to explore the everyday social practice of record keeping by those outside the recordkeeping disciplines in a contemporary public sector setting and it is only one of a few comparative case studies of record keeping practices. The findings show that there is no one accepted definition of record, rather what is considered a record will differ in each organizational setting. Each agency (or ) creates its own ‘shared practical understanding’ of records in their particular context. Site-specific cultural-discursive, material-economic and socio-political arrangements (the , and ) actively shape records and record keeping practices and the various affordances of records emphasised in that site. Additionally, across the Australian public sector and records creators do not find the language of records management accessible or useful. Creators of records also have their own internalised thresholds which they use to make judgements about records identification and capture. This study has demonstrated that records are active social practices, not simply passive and objective artefacts. Conceptualising records as social practices, in which humans and objects play an equal role, presents a paradigmatic shift for the recordkeeping disciplines that have privileged the artefact over the human elements of practices. The use of the practice theoretical approach provides a framework to produce significant and novel insights for researchers and practitioners in the recordkeeping disciplines

Regulation of glutamatergic signalling by PACAP in the mammalian suprachiasmatic nucleus

BACKGROUND: Previous studies indicate that light information reaches the suprachiasmatic nucleus (SCN) through a subpopulation of retinal ganglion cells that contain both glutamate and pituitary adenylyl cyclase activating peptide (PACAP). While the role of glutamate in this pathway has been well studied, the involvement of PACAP and its receptors are only beginning to be understood. Speculating that PACAP may function to modulate how neurons in the suprachiasmatic nucleus respond to glutamate, we used electrophysiological and calcium imaging tools to examine possible cellular interactions between these co-transmitters. RESULTS: Exogenous application of PACAP increased both the amplitude and frequency of spontaneous excitatory postsynaptic currents recorded from SCN neurons in a mouse brain slice preparation. PACAP also increased the magnitude of AMPA-evoked currents through a mechanism mediated by PAC1 receptors and the adenylyl cyclase-signalling cascade. This enhancement of excitatory currents was not limited to those evoked by AMPA as the magnitude of NMDA currents were also enhanced by application of PACAP. Furthermore, PACAP enhanced AMPA and NMDA evoked calcium transients while PACAP alone produced very little change in resting calcium in most mouse SCN neurons. Finally, in rat SCN neurons, exogenous PACAP enhanced AMPA evoked currents and calcium transients as well evoked robust calcium transients on its own. CONCLUSION: The results reported here show that PACAP is a potent modulator of glutamatergic signalling within the SCN in the early night