Biology subjects

Meyer, M. P.

Publications and source records attributed to Meyer, M. P..

8 recordsLinked to original sources

bioRxiv2026

Localization-dependent activation of the DEAD-box ATPase Vasa by eLOTUS domains

DEAD-box RNA helicases remodel RNA structures in many cellular pathways, yet how their activity is spatially controlled in cells remains poorly understood. The Drosophila germline helicase Vasa functions in ovaries only when localized to cytoplasmic granules, a process mediated by eLOTUS-domain proteins. Here, we define the mechanism by which eLOTUS domains activate Vasa. Biochemical analyses reveal that Vasa alone is largely inactive. eLOTUS domains bind the open conformation of Vasa and promote formation of the closed RNA- and ATP-bound state by accelerating RNA engagement. This stimulation requires a positively charged intrinsically disordered sequence within eLOTUS that increases RNA association. Mutations in this element abolish Vasa stimulation while preserving binding. We demonstrate that Vasa activation is essential in vivo. Together, these findings reveal a localization-dependent mechanism for regulating the DEAD-box helicase Vasa, in which enzymatic activity is gated by a spatially restricted cofactor.

biochemistry↗

bioRxiv2024

Reduced and Redundant: Information Processing of Prediction Errors during Sleep

During sleep, the human brain transitions to a sentinel processing mode, enabling the continued processing of environmental stimuli despite the absence of consciousness. Here, we employed advanced information-theoretic analyses, including mutual information (MI) and co-information (co-I), alongside event-related potential (ERP) and temporal generalization analyses (TGA), to characterize auditory prediction error processing across wakefulness and sleep. We hypothesized that a shared neural code would be present across sleep stages, with deeper sleep being associated with reduced information content and increased information redundancy. To investigate this, twenty-nine young healthy participants were exposed to an auditory local-global oddball paradigm during wakefulness and during an 8-hour sleep opportunity monitored via polysomnography in a cross-sectional study. We focused on local mismatch responses to a deviating fifth tone following four standard tones. ERP analyses showed that prediction error processing continued throughout all sleep stages (N1-N3, REM). Mutual information analyses revealed a substantial reduction in the amount of encoded prediction error information particularly during N3 and REM, although ERP amplitudes increased with deeper NREM sleep. In addition, we observed delayed information encoding during sleep and co-information analyses showed that neural dynamics became increasingly redundant with increasing sleep depth. Temporal generalisation analyses revealed a largely shared neural code between N2 and N3 sleep, although it differed between wakefulness and sleep. Here, we showed how the neural code of the sentinel processing mode changes from wake to light to deep sleep and REM, characterised by delayed processing, more redundant and less rich neural information in the human cortex as consciousness wanes. This altered stimulus processing reveals how neural information changes with the changes of consciousness states as we traverse the night.

neuroscience↗

bioRxiv2023

Spatial subdomains in the Optic Tectum for the encoding of visual information

1Neurons across the visual system provide estimates of the visual features they encode. However, the reliability of those estimates can vary across the neuronal population. Here, we use information theory to provide a spatial map of how well neurons can distinguish ethologically-relevant visual stimuli across the entire larval zebrafish optic tectum, a brain region responsible for driving visually guided behaviour. We find that the ability of neurons to discriminate between stimuli is non-uniformly distributed across the tectum. Specifically, we show that information about local motion is preferentially encoded in the posterior tectum, whilst information about whole-field motion is preferentially encoded in the anterior tectum. This is achieved through two systematic changes along the anterior-posterior axis of the tectum: (i) a change in the number of neurons that discriminate between stimuli and (ii) a change in how well each neuron can discriminate between stimuli. By classifying neurons into distinct subtypes based on their response properties we uncovered a small group of neurons that are spatially localised to specific regions of the tectum and are able to discriminate between visual stimuli in a highly reliable manner. Our results highlight the importance of implementing information theoretic approaches to assess visual responses and provide a novel description of regional specialisation in the zebrafish optic tectum.

neuroscience↗

bioRxiv2022

Light targeting the melanopic system suppresses melatonin, but does not alter sleepiness, vigilance, sensory processing, or sleep

Pre-sleep exposure to short-wavelength light suppresses melatonin and decreases sleepiness with activating effects extending to sleep. This has mainly been attributed to melanopic effects, but mechanistic insights are missing. Thus, we investigated whether two light conditions only differing in the melanopic effects (123 vs. 59 lux melanopic EDI) differentially affect sleep besides melatonin. Additionally, we studied whether the light differentially modulates sensory processing during wakefulness and sleep. Twenty-nine healthy volunteers (18-30 years, 15 women) were exposed to two metameric light conditions (high-vs. low-melanopic, {approx}60 photopic lux) for 1 hour ending 50 min prior to habitual bed time. This was followed by an 8-h sleep opportunity with polysomnography. Objective sleep measurements were complemented by self-report. Salivary melatonin, subjective sleepiness, and behavioural vigilance were sampled at regular intervals. Sensory processing was evaluated during light exposure and sleep on the basis of neural responses related to violations of expectations in an oddball paradigm. We observed suppression of melatonin by {approx}14 % in the high-compared to the low-melanopic condition. However, conditions did not differentially affect sleep, sleep quality, sleepiness, or vigilance. A neural mismatch response was evident during all sleep stages, but not differentially modulated by light. Suppression of melatonin by light targeting the melanopic system does not automatically translate to acutely altered levels of vigilance or sleepiness or to changes in sleep, sleep quality, or basic sensory processing. Given contradicting earlier findings and the retinal anatomy, this may suggest that an interaction between melanopsin and cone-rod signals needs to be considered. Statement of SignificanceMetameric light allows to mechanistically investigate the contribution of one specific retinal receptor. Using this approach, we here investigated the effects of high-vs. low-melanopic light for 1 hour in the evening at ecologically valid screen illuminance ({approx}60 photopic lux). Going beyond earlier research, we also investigated effects on sleep. We found that despite significant suppression of melatonin, other endpoints including sleep and sleep quality were not differentially affected. This underlines that melatonin suppression does not automatically translate to alterations of sleep, sleepiness, or vigilance. Further, it suggests that melanopsin effects may need to be studied in the context of cone-rod signals. Future research should thus investigate the relevance of such an interaction, which may vary between endpoints.

neuroscience↗

bioRxiv2021

Topographically localised modulation of tectal cell spatial tuning by natural scenes

Visual neurons can have their tuning properties contextually modulated by the presence of visual stimuli in the area surrounding their receptive field, especially when that stimuli contains natural features. However, stimuli presented in specific egocentric locations may have greater behavioural relevance, raising the possibility that the extent of contextual modulation may vary with position in visual space. To explore this possibility we utilised the small size and optical transparency of the larval zebrafish to describe the form and spatial arrangement of contextually modulated cells throughout an entire tectal hemisphere. We found that the spatial tuning of tectal neurons to a prey-like stimulus sharpens when the stimulus is presented in the context of a naturalistic visual scene. These neurons are confined to a spatially restricted region of the tectum and have receptive fields centred within a region of visual space in which the presence of prey preferentially triggers hunting behaviour. Our results demonstrate that circuits that support behaviourally relevant modulation of tectal neurons are not uniformly distributed. These findings add to the growing body of evidence that the tectum shows regional adaptations for behaviour.

neuroscience↗

bioRxiv2021

Single-cell Networks Reorganise to Facilitate Whole-brain Supercritical Dynamics During Epileptic Seizures

Excitation-inhibition (EI) balance may be required for the organisation of brain dynamics to a phase transition, criticality, which confers computational benefits. Brain pathology associated with EI imbalance may therefore occur due to a deviation from criticality. However, evidence linking critical dynamics with EI imbalance-induced pathology is lacking. Here, we studied the effect of EI imbalance-induced epileptic seizures on brain dynamics, using in vivo whole-brain 2-photon imaging of GCaMP6s larval zebrafish at single-neuron resolution. We demonstrate the importance of EI balance for criticality, with EI imbalance causing a loss of whole-brain critical statistics. Using network models we show that a reorganisation of network topology drives this loss of criticality. Seizure dynamics match theoretical predictions for networks driven away from a phase transition into disorder, with the emergence of chaos and a loss of network-mediated separation, dynamic range and metastability. These results demonstrate that EI imbalance drives a pathological deviation from criticality.

neuroscience↗

bioRxiv2019

Learning steers the ontogeny of an efficient hunting sequence in zebrafish larvae.

The success of goal-directed behaviours relies on the coordinated execution of a sequence of component actions. In young animals, such sequences may be poorly coordinated, but with age and experience, behaviour progressively adapts to efficiently exploit the animals ecological niche. How experience impinges on the developing neural circuits of behaviour is an open question. As a model system, larval zebrafish (Danio rerio) hold enormous potential for studying both the development of behaviour and the underlying circuits, but no relevant experience-dependent learning paradigm has yet been characterized. To address this, we have conducted a detailed study of the effects of experience on the ontogeny of hunting behaviour in larval zebrafish. We report that larvae with prior prey experience consume considerably more prey than naive larvae. This is mainly due to increased capture success that is also accompanied by a modest increase in hunt rate. We identified two components of the hunting sequence that are jointly modified by experience. At the onset of the hunting sequence, the orientation strategy of the turn towards prey is modified such that experienced larvae undershoot prey azimuth. Near the end of the hunt sequence, we find that experienced larvae are more likely to employ high-speed capture swims initiated from longer distances to prey. Combined, these modified turn and capture manoeuvrers can be used to predict the probability of capture success and suggest that their development provides advantages specific to larvae feeding on live-prey. Our findings establish an ethologically relevant paradigm in zebrafish for studying how the brain is shaped by experience to drive the ontogeny of efficient behaviour.

animal behavior and cognition↗

bioRxiv2018

Bayesian inference of neuronal ensembles

In many areas of the brain, both spontaneous and stimulus-evoked activity can manifest as synchronous activation of neuronal ensembles. The characterization of ensemble structure and dynamics provides important insights into how brain computations are distributed across neural networks. The proliferation of experimental techniques for recording the activity of neuronal ensembles calls for a comprehensive statistical method to describe, analyze and characterize these high dimensional datasets. Here we introduce a generative model of synchronous activity to describe spontaneously active neural ensembles. Unlike existing methods, our analysis provides a simultaneous estimation of ensemble composition, dynamics and statistical features of these neural populations, including ensemble noise and activity rate. We also introduce ensemble \"coherence\" as a measure of within-ensemble synchrony. We have used our method to characterize population activity throughout the tectum of larval zebrafish, allowing us to make statistical inference on the spatiotemporal organization of tectal ensembles, their composition and the logic of their interactions. We have also applied our method to functional imaging and neuropixels recordings from the mouse, allowing us to relate the activity of identified ensembles to specific behaviours such as running or changes in pupil diameter.

neuroscience↗