Multivariate analysis of electrophysiological diversity of Xenopus visual neurons during development and plasticity

Abstract Biophysical properties of neurons become increasingly diverse over development, but mechanisms underlying and constraining this diversity are not fully understood. Here we investigate electrophysiological characteristics of Xenopus tadpole midbrain neurons across development and during homeostatic plasticity induced by patterned visual stimulation. We show that in development tectal neuron properties not only change on average, but also become increasingly diverse. After sensory stimulation, both electrophysiological diversity and functional differentiation of cells are reduced. At the same time, the amount of cross-correlations between cell properties increase after patterned stimulation as a result of homeostatic plasticity. We show that tectal neurons with similar spiking profiles often have strikingly different electrophysiological properties, and demonstrate that changes in intrinsic excitability during development and in response to sensory stimulation are mediated by different underlying mechanisms. Overall, this analysis and the accompanying dataset provide a unique framework for further studies of network maturation in Xenopus tadpoles

Shift Work in Nurses: Contribution of Phenotypes and Genotypes to Adaptation

Daily cycles of sleep/wake, hormones, and physiological processes are often misaligned with behavioral patterns during shift work, leading to an increased risk of developing cardiovascular/metabolic/gastrointestinal disorders, some types of cancer, and mental disorders including depression and anxiety. It is unclear how sleep timing, chronotype, and circadian clock gene variation contribute to adaptation to shift work.Newly defined sleep strategies, chronotype, and genotype for polymorphisms in circadian clock genes were assessed in 388 hospital day- and night-shift nurses.Night-shift nurses who used sleep deprivation as a means to switch to and from diurnal sleep on work days (∼25%) were the most poorly adapted to their work schedule. Chronotype also influenced efficacy of adaptation. In addition, polymorphisms in CLOCK, NPAS2, PER2, and PER3 were significantly associated with outcomes such as alcohol/caffeine consumption and sleepiness, as well as sleep phase, inertia and duration in both single- and multi-locus models. Many of these results were specific to shift type suggesting an interaction between genotype and environment (in this case, shift work).Sleep strategy, chronotype, and genotype contribute to the adaptation of the circadian system to an environment that switches frequently and/or irregularly between different schedules of the light-dark cycle and social/workplace time. This study of shift work nurses illustrates how an environmental "stress" to the temporal organization of physiology and metabolism can have behavioral and health-related consequences. Because nurses are a key component of health care, these findings could have important implications for health-care policy

Pet-1 Deficiency Alters The Circadian Clock And Its Temporal Organization Of Behavior

The serotonin and circadian systems are two important interactive regulatory networks in the mammalian brain that regulate behavior and physiology in ways that are known to impact human mental health. Previous work on the interaction between these two systems suggests that serotonin modulates photic input to the central circadian clock (the suprachiasmatic nuclei; SCN) from the retina and serves as a signal for locomotor activity, novelty, and arousal to shift the SCN clock, but effects of disruption of serotonergic signaling from the raphe nuclei on circadian behavior and on SCN function are not fully characterized. In this study, we examined the effects on diurnal and circadian behavior, and on ex vivo molecular rhythms of the SCN, of genetic deficiency in Pet-1, an ETS transcription factor that is necessary to establish and maintain the serotonergic phenotype of raphe neurons. Pet-1-/- mice exhibit loss of rhythmic behavioral coherence and an extended daily activity duration, as well as changes in the molecular rhythms expressed by the clock, such that ex vivo SCN from Pet-1-/- mice exhibit period lengthening and sex-dependent changes in rhythmic amplitude. Together, our results indicate that Pet-1 regulation of raphe neuron serotonin phenotype contributes to the period, precision and light/dark partitioning of locomotor behavioral rhythms by the circadian clock through direct actions on the SCN clock itself, as well as through non-clock effects. © 2014 Ciarleglio et al

Data from: Multivariate analysis of electrophysiological diversity of Xenopus visual neurons during development and plasticity

Biophysical properties of neurons become increasingly diverse over development, but mechanisms underlying and constraining this diversity are not fully understood. Here we investigate electrophysiological characteristics of Xenopus tadpole midbrain neurons across development and during homeostatic plasticity induced by patterned visual stimulation. We show that in development tectal neuron properties not only change on average, but also become increasingly diverse. After sensory stimulation, both electrophysiological diversity and functional differentiation of cells are reduced. At the same time, the amount of cross-correlations between cell properties increase after patterned stimulation as a result of homeostatic plasticity. We show that tectal neurons with similar spiking profiles often have strikingly different electrophysiological properties, and demonstrate that changes in intrinsic excitability during development and in response to sensory stimulation are mediated by different underlying mechanisms. Overall, this analysis and the accompanying dataset provide a unique framework for further studies of network maturation in Xenopus tadpoles

Wheel open/lock circadian behavioral paradigms.

<p><b>a |</b> Double-plotted graphics representing two equal light cycle paradigms (12L:12D→DD) with opposite order of wheel access in each phase. <b>b |</b> Representative double-plotted actograms showing the monitored activity of mice that are, from <i>left</i> to <i>right</i>, wildtype, heterozygote, or knockout for <i>Pet-1</i>, as monitored by infrared (IR) motion detection (<i>top</i>) and wheel (<i>bottom</i>). Note that there is no wheel activity during wheel-locked phases. The <i>Pet-1</i>^+/+ mouse (<i>left</i>) represents paradigm A, while the <i>Pet-1</i>^+/− and <i>Pet-1</i>^−/− mice (<i>middle</i> and <i>right</i>, respectively) represents paradigm B. Y-axis represents days; X-axis represents time-of-day.</p

Averaged activity profiles across genotypes as monitored by (a) wheel and (b-d) infrared motion detector (IR) in LD.

<p>Each point represents the average across days and across animals within that particular genotype while in a 12L:12D cycle. Blue points represent <i>Pet-1</i>^+/+ mice; orange points represent <i>Pet-1</i>^+/− mice; black points represent <i>Pet-1</i>^−/− mice. Colored bar (<i>top</i>) represents 24 hour light cycle, where the grey is 12 hours of dark, and the yellow is 12 hours of light. Activity measured in revolutions/hour (a) or counts/hour (b–d). b | Overall IR activity profile of animals regardless of wheel state. These results are further broken-down into IR behavior with a free wheel (c) and with a locked wheel (d). See inset legend (a). Asterisks (*) denote significance at <i>p</i>≤0.05. Note the prominent early morning activity in <i>Pet-1</i>^−/− mice.</p

χ² periodogram analyses of genotype-specific and wheel-dependent effects on overall rhythmic amplitude (power) in LD (<i>top</i>) and DD (<i>bottom</i>).

<p>See inset legend (<i>top-left</i> panel) for genotype. Purple line represents significance at <i>p</i>≤0.05. Periodic component ratios measure the ratio of 12-hour:24-hour components on the wheel. Error bars represent SEM; asterisks (*) denote significance at <i>p</i>≤0.05.</p