Biology subjects

Kohler, M.

Publications and source records attributed to Kohler, M..

At least 19 recordsLinked to original sources

bioRxiv2024

From spreadsheet lab data templates to knowledge graphs: A FAIR data journey in the domain of AMR research

While awareness of FAIR (Findable, Accessible, Interoperable, and Reusable) principles has expanded across diverse domains, there remains a notable absence of impactful narratives regarding the practical application of FAIR data. This gap is particularly evident in the context of in-vitro and in-vivo experimental studies associated with the drug discovery and development process. Despite the structured nature of these data, reliance on classic methods such as spreadsheet-based visualization and analysis has limited the long-term reuse opportunities for such datasets. In response to this challenge, our work presents a representative journey towards FAIR data, characterized by structured, conventional spreadsheet-based lab data templates and the adoption of a knowledge graph framework for breaking data silos in the field of early antimicrobial resistance research. Here, we illustrate a tailored application of a "FAIRification framework" facilitating the practical implementation of FAIR principles. By showcasing the feasibility and benefits of transitioning to FAIR data practices, our work aims to encourage broader adoption and integration of FAIR principles within a research lab setting.

bioinformatics↗

bioRxiv2024

A Simple and Scalable Zebrafish Model of Sonic Hedgehog Medulloblastoma

Medulloblastoma (MB) is the most common malignant brain tumor in children and is stratified into three major subgroups. The Sonic hedgehog (SHH) subgroup represents [~]30% of all MB cases and has significant survival disparity depending upon TP53 status. Here, we describe the first zebrafish model of SHH MB using CRISPR to mutate ptch1, the primary genetic driver in human SHH MB. These tumors rapidly arise adjacent to the valvula cerebelli and resemble human SHH MB by histology and comparative genomics. In addition, ptch1-deficient MB tumors with loss of tp53 have aggressive tumor histology and significantly worse survival outcomes, comparable to human patients. The simplicity and scalability of the ptch1 MB model makes it highly amenable to CRISPR-based genome editing screens to identify genes required for SHH MB tumor formation in vivo, and here we identify the grk3 kinase as one such target.

cancer biology↗

bioRxiv2023

More than a prickly morphology: plastome variation in the prickly pear cacti (Opuntieae)

Plastid genomes (plastomes) have long been recognized as highly conserved in their overall structure, size, gene arrangement and content among land plants. However, recent studies have shown that some lineages present unusual variations in some of these features. Members of the cactus family are one of these lineages, with distinct plastome structures reported across disparate lineages including gene losses, inversions, boundary movements, or loss of the canonical inverted repeat (IR) region. Here, we further investigated plastome features of the tribe Opuntieae, the remarkable prickly pear cacti, which represent a diverse and important lineage of Cactaceae. We assembled the plastome of 43 species, representing a comprehensive sampling of the tribe including all seven genera. Plastomes varied considerably in length from 121 kbp to 162 kbp, with striking differences in the content and size of the IR region (contraction and expansion events), including the lack of the canonical IR in some lineages, and the pseudogenization or loss of some genes. Overall, nine different types of plastomes were reported deviating in the presence of the IR region or the genes contained in the IR. Plastomes sequences resolved phylogenetic relationships within major clades of Opuntieae but presented some contentious nodes depending on the data set analyzed (e.g., whole plastome vs. genes only). Incongruence analyses revealed that few plastome regions are supporting the most likely topology, while disputing topologies are driven by a handful of plastome markers, which may be the result of hard recalcitrant nodes in the phylogeny or by the lack of phylogenetic signal in certain markers. Our study reveals a dynamic nature of plastome evolution across closely related lineages, shedding light on peculiar features of cactus plastomes. Variation of plastome types across Opuntieae is remarkable in size, structure, and content, and can be important for the recognition of species in some major clades. Unraveling connections between the causes of plastome variation and the consequences on species biology, ecology, diversification, and adaptation, is a promising endeavor.

plant biology↗

bioRxiv2023

Temporal single-cell transcriptomic analysis of the sox1a:eGFP transgenic line identified the lateral floor plate progenitor cells as the origin of intraspinal serotonergic neurons

The Sox family of transcription factors plays a crucial role in the development of the vertebrate nervous system. In the zebrafish embryo, sox1 genes are expressed in neural progenitor cells and neurons of the ventral spinal cord. We recently reported that the loss of function of sox1a and sox1b leads to a significant decline in a subtype of V2 neurons, called V2s, in zebrafish. Here, a single-cell RNA sequencing approach was used to analyse the transcriptome of sox1a lineage progenitors and neurons in the zebrafish spinal cord at four different time points during the first five days of embryonic development, using the Tg(sox1a:eGFP) line. In addition to the previously described sox1a-expressing neurons, we found that sox1a is also expressed in late-developing intraspinal serotonergic neurons (ISNs). Analysis of developmental trajectories from single-cell data and depletion of lateral floor plate (LFP) cells by nkx2.9 morpholino knockdown suggest that ISNs arise from LFP precursor cells. Pharmacological inhibition of the Notch signalling pathway indicates that this pathway is required for the negative regulation of the development of LFP progenitor cells into ISN populations. Our results show that the zebrafish LFP is a precursor domain that longitudinally gives rise to ISNs in addition to the previously described KA" and V3 interneurons.

developmental biology↗

bioRxiv2022

Tracing the origin of Oriental beech stands across Western Europe and reporting hybridization with European beech - implications for assisted gene flow

Human-aided translocation of individuals within the species range, assisted gene flow (AGF), has been suggested as a climate change mitigation strategy, especially for foundational species, such as forest trees. The benefits and risks of AGF largely depend on the genetic divergence between host and donor populations, their rate and direction of hybridization, and the climate distance that the transfer involves. In this study, we explored the use of Oriental beech (Fagus sylvatica subsp. orientalis), growing from Iran to the Balkans, for AGF in populations of European beech (F. sylvatica subsp. sylvatica), which grow throughout Europe and are increasingly affected by climate warming. Using 16 microsatellite loci and samples from 13 and 6 natural populations of Oriental and European beech, respectively, we identified 5 distinct genetic clusters in Oriental beech with a divergence (FST) of 0.15 to 0.25 from European beech. Using this knowledge, we tracked the origin of 11 Oriental beech stands in Western Europe, some established in the early 1900s. In two stands of Greater Caucasus origin, we additionally genotyped offspring and found evidence for extensive hybridization, with 41.3% and 17.8% of the offspring having a hybrid status. Further, climate data revealed a higher degree of seasonality across the Oriental beech growing sites than across the planting sites in Western Europe, with some sites additionally having a warmer and drier climate. Accordingly, in one of these stands, we found evidence that bud burst of Oriental beech occurs four days earlier than in European beech. These results suggest that AGF of Oriental beech could increase the genetic diversity of European beech stands and may even help the introgression of variants that are more adapted to future climatic conditions. Our study showcases an evaluation of the benefits and risks of AGF and calls for similar studies on other native tree species.

evolutionary biology↗

bioRxiv2021

The BCM rule allows a spinal cord model to learn rhythmic movements

Animal locomotion is hypothesized to be controlled by a central pattern generator in the spinal cord. Experiments and models show that rhythm generating neurons and genetically determined network properties could sustain oscillatory output activity suitable for locomotion. However, current CPG models do not explain how a spinal cord circuitry, which has the same basic genetic plan across species, can adapt to control the different biomechanical properties and locomotion patterns existing in these species. Here we demonstrate that rhythmic and alternating movements in pendulum models can be learned by a monolayer spinal cord circuitry model using the BCM learning rule, which has been previously proposed to explain learning in the visual cortex. These results provide an alternative theory to CPG models, because rhythm generating neurons and genetically defined connectivity are not required in our model. Author summaryThe central pattern generator is the leading hypothesis of locomotor control in animals. There, rhythm generating neurons and genetically defined neural connectivity would form a circuit generating activity patterns suitable for locomotion. We provide a new hypothesis of locomotor control, where rhythmic patterns are learned by a Hebbian learning rule from a mechanical system that has an intrinsic tendency to oscillate.

neuroscience↗

bioRxiv2021

An Infant Sleep Electroencephalographic Marker of Thalamocortical Connectivity Predicts Behavioral Outcome in Late Infancy

Infancy represents a critical period during which thalamocortical brain connections develop and mature. Deviations in the maturation of thalamocortical connectivity are linked to neurodevelopmental disorders. There is a lack of early biomarkers to detect and localize neuromaturational deviations, which can be overcome with mapping through high-density electroencephalography (hdEEG) assessed in sleep. Specifically, slow waves and spindles in non-rapid eye movement (NREM) sleep are generated by the thalamocortical system, and their characteristics, slow wave slope and spindle density, are closely related to neuroplasticity and learning. Recent studies further suggest that information processing during sleep underlying sleep-dependent learning is promoted by the temporal coupling of slow waves and spindles, yet slow wave-spindle coupling remains unexplored in infancy. Thus, we evaluated three potential biomarkers: 1) slow wave slope, 2) spindle density, and 3) the temporal coupling of slow waves with spindles. We use hdEEG to first examine the occurrence and spatial distribution of these three EEG features in healthy infants and second to evaluate a predictive relationship with later behavioral outcomes. We report four key findings: First, infants EEG features appear locally: slow wave slope is maximal in occipital and frontal areas, whereas spindle density is most pronounced frontocentrally. Second, slow waves and spindles are temporally coupled in infancy, with maximal coupling strength in the occipital areas of the brain. Third, slow wave slope, spindle density, and slow wave-spindle coupling are not associated with concurrent behavioral status (6 months). Fourth, spindle density in central and frontocentral regions at age 6 months predicts later behavioral outcomes at 12 and 24 months. Neither slow wave slope nor slow wave-spindle coupling predict behavioral development. Our results propose spindle density as an early EEG biomarker for identifying thalamocortical maturation, which can potentially be used for early diagnosis of neurodevelopmental disorders in infants. These findings are complemented by our companion paper that demonstrates the linkage of spindle density to infant nighttime movement, framing the possible role of spindles in sensorimotor microcircuitry development. Together, our studies suggest that early sleep habits, thalamocortical maturation, and behavioral outcome are closely interwoven. A crucial next step will be to evaluate whether early therapeutic interventions may be effective to reverse deviations in identified individuals at risk. HighlightsO_LISlow waves and spindles occur in a temporally coupled manner in infancy C_LIO_LISlow wave slope, spindle density, and slow wave-spindle coupling are not related to concurrent behavioral development C_LIO_LISpindle density at 6 months predicts behavioral status at 12 and 24 months C_LIO_LISlow wave slope and slow wave-spindle coupling are not predictive of behavioral development C_LI

neuroscience↗

bioRxiv2021

Bedtime to the brain: How infants sleep habits intertwine with sleep neurophysiology

Adequate sleep is critical for development and facilitates the maturation of the neurophysiological circuitries at the basis of cognitive and behavioral function. Observational research has associated sleep problems in early life with worse later cognitive, psychosocial, and somatic health outcomes. Yet, the extent to which day-to-day sleep habits in early life relate to neurophysiology - acutely and long-term - remains to be explored. Here, we report that sleep habits in 32 healthy 6-month-olds assessed with actimetry are linked to fundamental aspects of their neurophysiology measured with high-density electroencephalography (hdEEG). Our study reveals four key findings: First, daytime sleep habits are linked to EEG slow wave activity (SWA). Second, habits of nighttime movement and awakenings from sleep are connected with spindle density. Third, habitual sleep timing is linked to neurophysiological connectivity quantified as Delta-coherence. And lastly, Delta-coherence at age 6 months predicts nighttime sleep duration at age 12 months. These novel findings widen our understanding that infants sleep habits are closely intertwined with three particular levels of neurophysiology: sleep pressure (determined by SWA), the maturation of the thalamocortical system (spindles), and the maturation of cortical connectivity (coherence). Our companion paper complements this insight in the perspective of later developmental outcomes: early thalamocortical connectivity (spindle density) at age 6 months predicts later behavioural status at 12 and 24 months. The crucial next step is to extend this concept to clinical groups to objectively characterize infants sleep habits "at risk" that foster later neurodevelopmental problems. HighlightsO_LIInfants habitual sleep behavior (actimetry) is linked with their sleep neurophysiology (EEG) C_LIO_LIHabits of daytime sleeping (naps) are related to slow wave activity C_LIO_LIInfants movements and awakenings at nighttime are linked to their sleep spindles C_LIO_LISleep timing (infants bedtimes) is associated with cortical connectivity in the EEG C_LI

neuroscience↗

bioRxiv2021

Diversified physiological sensory input connectivity questions the existence of distinct classes of spinal interneurons in the adult cat in vivo

The spinal cord is engaged in all forms of motor performance but its functions are far from understood. Because network connectivity defines function, we explored the connectivity for muscular, tendon and tactile sensory inputs among a wide population of spinal interneurons in the lower cervical segments. Using low noise intracellular whole cell recordings in the decerebrated, nonanesthetized cat in vivo, we could define mono-, di-, trisynaptic inputs as well as the weights of each input. Whereas each neuron had a highly specific input, and each indirect input could moreover be explained by inputs in other recorded neurons, we unexpectedly also found the input connectivity of the spinal interneuron population to form a continuum. Our data hence contrasts with the currently widespread notion of distinct classes of interneurons. We argue that this suggested diversified physiological connectivity, which likely requires a major component of circuitry learning, implies a more flexible functionality. 1. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY 2. HighlightsO_LIIn vivo whole cell, intracellular recording of spinal interneurons. C_LIO_LIPatterns of input from Ia, Ib and cutaneous afferents is highly diversified. C_LIO_LILearning appears to be a defining factor of spinal interneuron connectivity. C_LI

neuroscience↗

bioRxiv2021

Additive Effects of Cognitive Load, Motor Demand, and Environmental Complexity on Attention: A Real-World EEG-study

The capacity to regulate ones attention in accordance with fluctuating task demands and environmental contexts is an essential feature of adaptive behavior. Although the electrophysiological correlates of attentional processing have been extensively studied in the laboratory, relatively little is known about the way they unfold under more variable, ecologically-valid conditions. Accordingly, this study employed a real-world EEG design to investigate how attentional processing varies under increasing cognitive, motor, and environmental demands. Forty-four participants were exposed to an auditory oddball task while (1) sitting in a quiet room inside the lab, (2) walking around a sports field, and (3) wayfinding across a university campus. In each condition, participants were instructed to either count or ignore oddball stimuli. While behavioral performance was similar across the lab and field conditions, oddball count accuracy was significantly reduced in the campus condition. Moreover, event-related potential components (mismatch negativity and P3) elicited in both real-world settings differed significantly from those obtained under laboratory conditions. These findings demonstrate the impact of environmental factors on attentional processing during simultaneously-performed motor and cognitive tasks, highlighting the value of incorporating dynamic and unpredictable contexts within naturalistic designs.

neuroscience↗

bioRxiv2020

Which are the central aspects of infant sleep? Thedynamic of sleep composites across infancy

Sleep is ubiquitous during infancy and important for the well-being of both infant and parent. Therefore, there is large interest to characterize infant sleep with reliable tools, for example by means of combining actigraphy with 24-h-diaries. However, it is critical to select the right variables to characterize sleep. With a principal component analysis, we identified 5 underlying sleep composites from 48 commonly used sleep variables: Sleep Night, Sleep Day, Sleep Activity, Sleep Timing and Sleep Variability. These composites accurately reflect the known changes of sleep throughout infancy as Sleep Day (representing naps), Sleep Activity (representing sleep efficiency and consolidation) and Sleep Variability (representing day-to-day stability) decrease across infancy, while Sleep Night (representing nighttime sleep) slightly increases and Sleep Timing becomes earlier with increasing age. Additionally, we uncover interesting dynamics between the sleep composites and demonstrate that infant sleep is not only highly variable between infants but also considerably dynamic within infants across time. Interestingly, Sleep Day is associated with behavioral development and therefore a potential marker for maturation. We recommend the use of sleep composites or of those specific single variables, which are solid representatives of the sleep composites for more reliable research.

neuroscience↗

bioRxiv2020

Variation in transparency degree: response to light availability or part of mimicry syndrome?

Transparency reduces prey detectability by predators. While transparent aquatic species hold higher transparency levels as the light availability of their habitat increases, less is known about such variation in terrestrial species. Lepidoptera species exhibiting transparent wings display various levels of transparency. Using two complementary approaches, we explore how the evolution of different transparency degrees relates to habitat openness, activity rhythm and mimicry syndrome (bee/wasp versus dead-leaf mimic). First, by exposing artificial moth-like prey to wild avian predators in a range of habitat openness, we show that survival is lower in more open habitats. We also found that less transparent morphs are more attacked than more transparent ones, regardless of habitat openness degree. Second, by analysing the evolution of wing features and ecological traits in 107 clearwing species, we found that diurnal species transmit more light than nocturnal species under certain conditions (when considering only forewings, at smaller clearwing surfaces and at larger wing lengths) and that species flying in open habitats and exhibiting large percentages of clearwing surface transmit slightly more light than those flying in closed habitats, although this is reversed at smaller percentages of clearwing surfaces. Additionally, bee/wasp mimics are more often diurnal and have higher and less variable light transmittances than dead-leaf mimics, which are more often nocturnal. Flying during the day, in open habitats and mimicking insects with transparent wings seem to promote high light transmittance under certain circumstances. Activity rhythm, habitat openness and species interactions play a crucial role in determining transparency design on land.

evolutionary biology↗

bioRxiv2020

Neuronal leak within recurrent neuronal networks prevents the generation of high frequency spurious signals

Recurrent circuitry components are distributed widely within the brain, including both excitatory and inhibitory synaptic connections. Recurrent neuronal networks have potential stability problems, perhaps a predisposition to epilepsy. More generally, instability risks making internal representations of information unreliable. To assess the inherent stability properties of such recurrent networks, we tested a linear summation, non-spiking neuron model with and without a dynamic leak, corresponding to the low-pass filtering of synaptic input current by the RC circuit of the biological membrane. We first show that the output of this neuron model, in either of its two forms, follows its input at a higher fidelity than a wide range of spiking neuron models across a range of input frequencies. Then we constructed fully connected recurrent networks with equal numbers of excitatory and inhibitory neurons and randomly distributed weights across all synapses. When the networks were driven by pseudorandom sensory inputs with varying frequency, the recurrent network activity tended to induce high frequency self-amplifying components, sometimes evident as distinct transients, which were not present in the input data. The addition of a dynamic leak based on known membrane properties consistently removed such spurious high frequency noise across all networks. Furthermore, we found that the neuron model with dynamic leak imparts a network stability that seamlessly scales with the size of the network, conduction delays, the input density of the sensory signal and a wide range of synaptic weight distributions. Our findings suggest that neuronal dynamic leak serves the beneficial function of protecting recurrent neuronal circuitry from the self-induction of spurious high frequency signals, thereby permitting the brain to utilize this architectural circuitry component regardless of network size or recurrency. Author SummaryIt is known that neurons of the brain are extensively interconnected, which can result in many recurrent loops within its neuronal network. Such loops are prone to instability. Here we wanted to explore the potential noise and instability that could result in recurrently connected neuronal networks across a range of conditions. To facilitate such simulations, we developed a non-spiking neuron model that captures the main characteristics of conductance-based neuron models of Hodgkin-Huxley type, but is more computationally efficient. We found that a so-called dynamic leak, which is a natural consequence of the way the membrane of the neuron is constructed and how the neuron integrates synaptic inputs, provided protection against spurious, high frequency noise that tended to arise in our recurrent networks of varying size. We propose that this linear summation model provides a stable and useful tool for exploring the computational behavior of recurrent neural networks.

neuroscience↗

bioRxiv2020

Insights into chloroplast genome variation across Opuntioideae (Cactaceae)

Chloroplast genomes (plastomes) are frequently treated as highly conserved among land plants. However, many lineages of vascular plants have experienced extensive structural rearrangements, including inversions and modifications to the size and content of genes. Cacti are one of these lineages, containing the smallest plastome known for an obligately photosynthetic angiosperm, including the loss of one copy of the inverted repeat ([~]25 kb) and the ndh genes suite, but only a few cacti from the subfamily Cactoideae have been sufficiently characterized. Here, we investigated the variation of plastome sequences across the second-major lineage of the Cactaceae, the subfamily Opuntioideae, to address 1) how variable is the content and arrangement of chloroplast genome sequences across the subfamily, and 2) how phylogenetically informative are the plastome sequences for resolving major relationships among the clades of Opuntioideae. Our de novo assembly of the Opuntia quimilo plastome recovered an organelle of 150,347 bp in length with both copies of the inverted repeats and the presence of all the ndh genes suite. An expansion of the large single copy unit and a reduction of the small single copy was observed, including translocations and inversion of genes as well as the putative pseudogenization of numerous loci. Comparative analyses among all clades within Opuntioideae suggested that plastome structure and content vary across taxa of this subfamily, with putative independent losses of the ndh gene suite and pseudogenization of genes across disparate lineages, further demonstrating the dynamic nature of plastomes in Cactaceae. Our plastome dataset was robust in determining relationships among major clades and subclades within Opuntioideae, resolving three tribes with high support: Cylindropuntieae, Tephrocacteae and Opuntieae. A plastome-wide survey for highly informative phylogenetic markers revealed previously unused regions for future use in Sanger-based studies, presenting a valuable dataset with primers designed for continued evolutionary studies across Cactaceae. These results bring new insights into the evolution of plastomes in cacti, suggesting that further analyses should be carried out to address how ecological drivers, physiological constraints and morphological traits of cacti may be related with the common rearrangements in plastomes that have been reported across the family.

evolutionary biology↗

bioRxiv2020

Beyond endemism, expanding conservation efforts: a relictual Pleistocene distribution and first report of the prickly pear cactus, Opuntia bonaerensis, in Brazil and Uruguay

Geographical range is one of the critical features for species conservation assessment. Nevertheless, species distribution is frequently unknown, undervalued or overlooked. During a broad taxonomic and floristic study of the southern South American prickly pear species (Opuntia spp.), new records of a previously endemic Argentinian taxon have been found in Uruguay and Brazil. Molecular phylogenetic inference was carried out to further evaluate the identity of the new records, and ecological niche models were implemented to test how the new records would fit in the previous known distribution of the species. Through molecular and morphological evidence, we confirmed the new records of Opuntia bonaerensis for Brazilian and Uruguayan floras and discussed its phylogenetic relationship and morphologic similarities with closely related species. Our new records uncovered a distributional pattern congruent with the Neotropical Peripampasic Orogenic Arc, which must be further explored to better determine the biogeographic history of the species. Ecological niche models (ENM) revealed that O. bonaerensis had a putative ancient distribution across the grasslands and shrublands in the Pampean region largely congruent with the populations found in Brazil and Uruguay, suggesting relictual Pleistocene populations of the species and the role of glacial/interglacial cycles on the distribution of the species. In a prospective climate change scenario, ENM suggests that the species would in general be more restricted to the southernmost limits of the Pampa region and previous outlying records from Mendoza (Argentina) are a putative future refuge for O. bonaerensis. The importance of these new records for biodiversity and conservation assessment efforts that are ongoing at different scales in Brazil and neighbor areas is highlighted.

plant biology↗

bioRxiv2020

Reassessment and typification of Opuntia canterae (Opuntioideae, Cactaceae), an endemic prickly-pear cactus of Uruguay

Background and aimsOpuntia is the most widespread genus of Cactaceae, naturally occurring throughout arid and semi-arid areas of the Americas. Many of the species have taxonomic problems owed to incomplete original descriptions, lack of type designations, a paucity of taxonomic revisions and in general, difficult species delimitation resulting from hybridization, morphological plasticity and poor specimen preparation. However, efforts are being undertaken to fill in the gaps in our distributional, morphological and phylogenetic knowledge of the group. Here, we reassess the name Opuntia canterae, providing an updated description, typification, photographs, distribution map, conservation assessment and additional notes. Material and methodsExtensive fieldwork was conducted, along with comprehensive herbarium and literature review. Morphological characters were assessed based on the commonly used characters used for prickly pears. Species delimitation is proposed based on our morphological studies, taxonomic and literature revision, as well as preliminary phylogenetic studies. The IUCN guidelines were followed to provide a conservation assessment of the species. Key resultsOpuntia canterae is reassessed as a distinct species separated from its previous synonym (O. elata) by the elliptic to long-oblanceolate stem segments, acute to conical flower bud apex and long-obconic fruits. An epitype is here designate for purposes of the precise designation of the name to the taxon. The species is considered endemic to Uruguay and is assessed as Vulnerable (VU) using IUCN criteria, but more fieldwork will be necessary to provide a more precise conservation status.

plant biology↗

bioRxiv2019

Biological data questions the support of the self inhibition required for pattern generation in the half center model.

Locomotion control in mammals has been hypothesized to be governed by a central pattern generator (CPG) located in the circuitry of the spinal cord. The most common model of the CPG is the half center model, where two pools of neurons generate alternating, oscillatory activity. In this model, the pools reciprocally inhibit each other ensuring alternating activity. There is experimental support for reciprocal inhibition. However another crucial part of the half center model is a self inhibitory mechanism which prevents the neurons of each individual pool from infinite firing. Self-inhibition is hence necessary to obtain alternating activity. But critical parts of the experimental bases for the proposed mechanisms for self-inhibition were obtained in vitro, in preparations of juvenile animals. The commonly used adaptation of spike firing does not appear to be present in adult animals in vivo. We therefore modeled several possible self inhibitory mechanisms for locomotor control. Based on currently published data, previously proposed hypotheses of the self inhibitory mechanism, necessary to support the CPG hypothesis, seems to be put into question by functional evaluation tests or by in vivo data. This opens for alternative explanations of how locomotion activity patterns in the adult mammal could be generated. Author summaryLocomotion control in animals is hypothesized to be controlled through an intrinsic central pattern generator in the spinal cord. This was proposed over a hundred years ago and has subsequently been formed into a consistent theory, through experimentation and computer modeling. However, critical data that support the neuronal circuitry mechanisms underpinning this theory has been obtained in experiments that greatly differ from intact animals. We propose, after trying to fill in this critical part, that new ideas are required to explain locomotion of intact animals.

neuroscience↗

bioRxiv2018

Actimetry in infant sleep research: an approach to facilitate comparability

Study ObjectivesOnly standardized objective assessments reliably capture the large variability of sleep behavior in infancy, which is the most pronounced during the human lifespan. This is important for clinical as well as basic research. Actimetry is a cost-efficient method to objectively track infant sleep/wake behavior by assessing limb movements. Nevertheless, the standardization of actimetry-based sleep/wake measures is limited by two factors: the use of different computational approaches and the bias towards measuring only nighttime sleep - neglecting [~]20 % of sleep infants obtain during daytime.\n\nMethodsWe used actimetry in 50 infants for 10 continuous days at ages 3, 6 and 12 mo in a longitudinal approach. We analyzed the infants sleep/wake behaviors applying with two commonly used algorithms: Sadeh and Oakley/Respironics. We compared minute-by-minute agreement and Kappa between the two algorithms, as well as the algorithms with sleep/wake measures from a comprehensive 24-hour, parent-reported diary.\n\nResultsAgreement between uncorrected algorithms was moderate (77 - 84%). By introducing a 6-step adjustment, we increased agreement between algorithms (96 - 97%) and with the diary. This decreased the difference between the two algorithms in e.g. Total Sleep Duration from 4.5 h to 0.2 h.\n\nConclusionsThis computational pipeline enhances comparability between infant actimetry studies and the inclusion of parent-reported diaries allows the integration of daytime sleep. Objectively assessed infant sleep that is comparable across different studies supports the establishment of normative developmental trajectories and clinical cutoffs.

neuroscience↗