Sleep is critical for proper memory consolidation. The locus coeruleus (LC) releases norepinephrine throughout the brain except when the LC falls silent throughout rapid eye movement (REM) sleep and prior to each non-REM (NREM) sleep spindle. We hypothesize that these transient LC silences allow the synaptic plasticity that is necessary to incorporate new information into pre-existing memory circuits. We found that spontaneous LC activity within sleep spindles triggers a decrease in spindle power. By optogenetically stimulating norepinephrine-containing LC neurons at 2 Hz during sleep, we reduced sleep spindle occurrence, as well as NREM delta power and REM theta power, without causing arousals or changing sleep amounts. Stimulating the LC during sleep following a hippocampus-dependent food location learning task interfered with consolidation of newly learned locations and reconsolidation of previous locations, disrupting next-day place cell activity. The LC stimulation-induced reduction in NREM sleep spindles, delta, and REM theta and reduced ripple-spindle coupling all correlated with decreased hippocampus-dependent performance on the task. Thus, periods of LC silence during sleep following learning are essential for normal spindle generation, delta and theta power, and consolidation of spatial memories.

Learning-activated engram neurons play a critical role in memory recall. An untested hypothesis is that these same neurons play an instructive role in offline memory consolidation. Here we show that a visually-cued fear memory is consolidated during post-conditioning sleep in mice. We then use TRAP (targeted recombination in active populations) to genetically label or optogenetically manipulate primary visual cortex (V1) neurons responsive to the visual cue. Following fear conditioning, mice respond to activation of this visual engram population in a manner similar to visual presentation of fear cues. Cue-responsive neurons are selectively reactivated in V1 during post-conditioning sleep. Mimicking visual engram reactivation optogenetically leads to increased representation of the visual cue in V1. Optogenetic inhibition of the engram population during post-conditioning sleep disrupts consolidation of fear memory. We conclude that selective sleep-associated reactivation of learning-activated sensory populations serves as a necessary instructive mechanism for memory consolidation.

Sleep impacts diverse physiological and neural processes and is itself affected by the menstrual cycle; however, few studies have examined the effects of the estrous cycle on sleep in rodents. Studies of disease mechanisms in females therefore lack critical information regarding estrous cycle influences on relevant sleep characteristics. We recorded electroencephalographic (EEG) activity from multiple brain regions to assess sleep states as well as sleep traits such as spectral power and interregional spectral coherence in freely cycling females across the estrous cycle and compared with males. Our findings show that the high hormone phase of proestrus decreases the amount of nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep and increases the amount of time spent awake compared with other estrous phases and to males. This spontaneous sleep deprivation of proestrus was followed by a sleep rebound in estrus which increased NREM and REM sleep. In proestrus, spectral power increased in the delta (0.5–4 Hz) and the gamma (30–60 Hz) ranges during NREM sleep, and increased in the theta range (5–9 Hz) during REM sleep during both proestrus and estrus. Slow-wave activity (SWA) and cortical sleep spindle density also increased in NREM sleep during proestrus. Finally, interregional NREM and REM spectral coherence increased during proestrus. This work demonstrates that the estrous cycle affects more facets of sleep than previously thought and reveals both sex differences in features of the sleep–wake cycle related to estrous phase that likely impact the myriad physiological processes influenced by sleep.

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Abstract. The quality of data derived from primary healthcare electronic systems has been subjected to little critical systematic analysis, especially in relation to the purported benefits and substantial investment in electronic information systems in primary care. Many indicators of quality of care are based on numbers of certain types of patients as denominators. Consistency of denominator data is vital for comparison of indicators over time and between services. This paper examines the consistency of denominator data extracted from electronic health records (EHRs) for monitoring of access and quality of primary health care. Data collection and analysis were conducted as part of a prospective mixed-methods formative evaluation of the Commonwealth Government's Indigenous Chronic Disease Package. Twenty-six general practices and 14 Aboriginal Health Services (AHSs) located in all Australian States and Territories and in urban, regional and remote locations were purposively selected within geographically defined locations. Percentage change in reported number of regular patients in general practices ranged between -50% and 453% (average 37%). The corresponding figure for AHSs was 1% to 217% (average 31%). In approximately half of general practices and AHSs, the change was 20%. There were similarly large changes in reported numbers of patients with a diagnosis of diabetes or coronary heart disease (CHD), and Indigenous patients. Inconsistencies in reported numbers were due primarily to limited capability of staff in many general practices and AHSs to accurately enter, manage, and extract data from EHRs. The inconsistencies in data required for the calculation of many key indicators of access and quality of care places serious constraints on the meaningful use of data extracted from EHRs. There is a need for greater attention to quality of denominator data in order to realise the potential benefits of EHRs for patient care, service planning, improvement, and policy. We propose a quality improvement approach for enhancing data quality.Additional keywords: clinical information systems, electronic data extraction, primary health care, quality indicators, quality of data.

We developed a method to evaluate bovine sperm membranes in normal (1G) and simulated microgravity (Sim-µG). Bovine spermatozoa are used as a model system because they have cellular membranes analogous to those of other cell types, and yet are much simpler because they have no cytoplasm and do not participate in DNA transcription or mRNA translation. They can be cultured as single cells and are easily evaluated for membrane characteristics using flow cytometry. These features make the mammalian spermatozoon a useful model for exploring the principles of membrane structure/function in the presence of a variety of environmental challenges such as simulated microgravity. Cryopreserved, washed beef bull sperm (4-8 × 106 mL −1 ) were incubated under non-capacitating conditions (modified glucose-free Tyrode's medium containing low bicarbonate, HEPES buffer, pyruvate and 3 mg mL −1 BSA V; 23 • C in air), and these spermatozoa remained alive for 24-48 h at 1G. To simulate µG, spermatozoa were incubated under the same conditions, in a HARV 10 rotating wall vessel (RWV, Synthecon, Inc, Houston,TX, USA) at 9 rpms. Spermatozoa were incubated in 1G and Sim-µG environments for 2.5-4.5 h and subsequently exposed to 0, 60 or 80 µg mL −1 LC for 0, 4, 8, 12, 16 and 20 min. Three fluorochrome combinations were used as probes at each [LC]/time point: (1) propidium Iodide (dead status) + SYBR 14 (live status);(2) PI + FITC-PSA (acrosome reactions [ARs]); (3) PI + MitoTracker Deep Red (mitochondrial activity). Approximately 1 million spermatozoa from 3 bulls were evaluated over 4 days. Data were acquired on a FACSVantage SE flow cytometer, and initially analyzed (quality control) using the bundled FACSVantage SE software package (Cell Quest, BD BioSciences, San Jose, CA, USA). This provided graphics of simple cell relations (fluorescence v. LC exposure time). For further statistical analysis, and incorporation of non-parametric statistical tools (including pattern recognition using Support Vector Machines), the data were processed using a collection of Perl scripts and C programs. Results: Live/dead status: When Sim-µG + 60 µg mL −1 LC sperm were compared to 1G + 60 µg mL −1 LC, and 80 µg mL −1 LC sperm, their profiles were more similar to the 1G 80 µg mL −1 LC profiles. AR status: the Sim-µG + 60 µg mL −1 LC profiles were similar to the 1G + 60 µg mL −1 LC profiles. Mitochondrial Status: the Sim-µG + 60 µg mL −1 LC profiles were more similar to 1G + 80 µg mL −1 LC profiles. Summary: although Sim-µG sperm lost their motility within 3 h, they were alive. Cell profiles indicate that Sim-µG sperm nuclear membranes are less stable and their mitochondria are less functional than the 1G controls, but their acrosomes are intact indicating that fertilizing potential may remain. Additional experiments are needed to determine the time course for Sim-µG, induced changes, and whether Sim-µG sperm can penetrate eggs.

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