Biology subjects

Robson, D. N.

Publications and source records attributed to Robson, D. N..

5 recordsLinked to original sources

bioRxiv2026

Usherin in the pineal gland: altered sleep in zebrafish models of Usher syndrome type 2a

Usher syndrome type 2A (USH2a), the most common form of hereditary deaf-blindness, is frequently accompanied by fatigue and poor sleep quality. As these sleep problems occur independently of visual decline, it is hypothesized that the USH2A-encoded protein usherin regulates sleep and circadian rhythmicity via an extra-retinal mechanism. Ush2a knockout zebrafish models were utilized to investigate this hypothesis. Immunohistochemical analysis demonstrated usherin localisation in pineal gland photoreceptor cells in wild-type larvae, alongside the USH2 complex proteins Adgrv1 and Whrna. Cross-species transcriptomic and proteomic analyses confirmed USH2A expression in all mammalian pineal gland tissues studied. Circadian clock gene expression was measured over 24 h and showed preserved oscillatory patterns in wild-type and mutant zebrafish. Ex vivo superfusion of pineal glands revealed sustained circadian melatonin release with comparable phase and period to controls, although potential differences in absolute melatonin levels could not be excluded. Despite intact clock gene expression and melatonin release in ush2a mutants, behavioural classification over 24-h recordings revealed altered sleep-wake behaviour: ush2a mutants displayed elevated daytime sleep and significantly prolonged and more variable sleep latency. The dissociation between intact molecular rhythms and abnormal sleep behaviour likely implicates that usherin plays a role in sleep-wake regulation independent of the circadian pacemaker and melatonin synthesis. These findings suggest a novel role of usherin in the pineal gland and establish a mechanistic link between usherin dysfunction and sleep disturbances, providing a biological basis for the fatigue and sleep problems reported in USH2a patients.

animal behavior and cognition↗

bioRxiv2023

A population code for spatial representation in the larval zebrafish telencephalon

The vertebrate telencephalon is the site of complex cognitive processes, such as spatial cognition. The larval zebrafish telencephalon is a compact circuit of only [~]10,000 neurons that contains potentially homologous structures to the mammalian basal ganglia and limbic system (e.g., the hippocampus). However, despite long-standing evidence that spatial navigation and learning in zebrafish requires an intact telencephalon, cells believed to underlie spatial cognition in the mammalian hippocampus (e.g., place cells) have yet to be established in any fish species. Using a tracking microscope to image brain-wide activity at cellular resolution in freely swimming larval zebrafish, we compute the spatial information of neurons throughout the zebrafish brain. Strikingly, in every animal we recorded, cells with the highest spatial specificity are enriched in the zebrafish telencephalon. These cells form a population code of space, from which we can decode the animals spatial location across time. By continuous recording of population-level activity, we find that the activity manifold of place cells gradually untangles over time. Through systematic manipulation of allothetic and idiothetic cues, we demonstrate that place cells in the zebrafish telencephalon integrate multiple sources of information. By analysis of neighborhood distance between cells across environments, we find that the spatial representation in the zebrafish telencephalon partially generalizes across environments, suggesting that preconfigured network states may have been a feature of spatial computation that emerged early in vertebrate evolution.

neuroscience↗

bioRxiv2023

Neural and behavioral organization of rapid eye movement sleep in zebrafish

Sleep is ubiquitous across the animal kingdom. However, the definition for sleep varies significantly across species. In organisms such as C. elegans, Drosophila, and zebrafish, sleep is classically defined as periods of locomotor quiescence with an increased arousal threshold1-6. In mammals, sleep is further subdivided into rapid eye movement (REM) and non-rapid eye movement (NREM) sleep, but the evolutionary origin of these two sleep states remains unclear7-12. Using longitudinal, high-resolution imaging of naturalistic sleep-wake behavior, we find that the classical definition of larval zebrafish sleep encompasses two clearly distinct quiescent states, one with rapid eye movements (qREM) and one without rapid eye movements (qNREM). Remarkably, qREM states are maintained in congenitally blind larval zebrafish, suggesting that qREM emerged during vertebrate evolution not as a response to internally generated visual imagery (i.e., the "scanning hypothesis")13, but potentially as a strategy to maintain oculomotor stimulation during rest14. Lastly, using brain-wide imaging in freely swimming animals, we find that, in contrast to fixed point attractor models of sleep developed in invertebrates15, population-level activity during zebrafish qREM unfolds along smooth committed trajectories through state-space. This work suggests a significant rethinking of the behavioral and neural organization of sleep in early vertebrates and the emergence of REM during vertebrate evolution.

neuroscience↗

bioRxiv2017

A brain wide circuit model of heat evoked swimming behavior in larval zebrafish

Thermosensation provides crucial information but it is poorly understood how temperature representation is transformed from sensation to behavior. Here, we report a preparation that allows control of heat delivery to zebrafish larvae while monitoring motor output and imaging whole-brain calcium signals, thereby uncovering algorithmic and computational rules that couple dynamics of heat modulation, neural activity and swimming behavior. This approach identifies a critical step in the transformation of temperature representation between the sensory trigeminal ganglia and the hindbrain: A simple sustained trigeminal stimulus representation is transformed into a representation of absolute temperature as well as temperature changes in the hindbrain that explains the observed motor output. An activity constrained dynamic circuit model captures the most prominent aspects of these sensori-motor transformations and predicts both behavior and neural activity in response to novel heat stimuli. These findings provide the first algorithmic description of heat processing from sensory input to behavioral output.

neuroscience↗

bioRxiv2017

Gaze-stabilizing central vestibular neurons project asymmetrically to extraocular motoneuron pools

Within reflex circuits, specific anatomical projections allow central neurons to relay sensations to effectors that generate movements. A major challenge is to relate anatomical features of central neural populations -- such as asymmetric connectivity -- to the computations the populations perform. To address this problem, we mapped the anatomy, modeled the function, and discovered a new behavioral role for a genetically-defined population of central vestibular neurons in rhombomeres 5-7 of larval zebrafish. First, we found that neurons within this central population project preferentially to motoneurons that move the eyes downward. Concor-dantly, when the entire population of asymmetrically-projecting neurons was stimulated collectively, only downward eye rotations were observed, demonstrating a functional correlate of the anatomical bias. When these neurons are ablated, fish failed to rotate their eyes following either nose-up or nose-down body tilts. This asymmetrically-projecting central population thus participates in both up and downward gaze stabilization. In addition to projecting to motoneurons, central vestibular neurons also receive direct sensory input from peripheral afferents. To infer whether asymmetric projections can facilitate sensory encoding or motor output, we modeled differentially-projecting sets of central vestibular neurons. Whereas motor command strength was independent of projection allocation, asymmetric projections enabled more accurate representation of nose-up stimuli. The model shows how asymmetric connectivity could enhance the representation of imbalance during nose-up postures while preserving gaze-stabilization performance. Finally, we found that central vestibular neurons were necessary for a vital behavior requiring maintenance of a nose-up posture: swim bladder inflation. These observations suggest that asymmetric connectivity in the vestibular system facilitates representation of ethologically-relevant stimuli without compromising reflexive behavior.\n\nSignificance StatementInterneuron populations use specific anatomical projections to transform sensations into reflexive actions. Here we examined how the anatomical composition of a genetically-defined population of balance interneurons in the larval zebrafish relates to the computations it performs. First, we found that the population of interneurons that stabilize gaze preferentially project to motoneurons that move the eyes downward. Next, we discovered through modeling that such projection patterns can enhance the encoding of nose-up sensations without compromising gaze stabilization. Finally we found that loss of these interneurons impairs a vital behavior, swim bladder inflation, that relies on maintaining a nose-up posture. These observations suggest that anatomical specialization permits neural circuits to represent relevant features of the environment without compromising behavior.

neuroscience↗