Biology subjects

Herrera, K. J.

Publications and source records attributed to Herrera, K. J..

9 recordsLinked to original sources

bioRxiv2025

Fishexplorer: A multimodal cellular atlas platform for neuronal circuit dissection in larval zebrafish

Understanding how neural circuits give rise to behavior requires comprehensive knowledge of neuronal morphology, connectivity, and function. Atlas platforms play a critical role in enabling the visualization, exploration, and dissemination of such information. Here, we present FishExplorer, an interactive and expandable community platform designed to integrate and analyze multimodal brain data from larval zebrafish. FishExplorer supports datasets acquired through light microscopy (LM), electron microscopy (EM), and X-ray imaging, all co-registered within a unified spatial coordinate system which enables seamless comparison of neuronal morphologies and synaptic connections. To further assist circuit analysis, FishExplorer includes a suite of tools for querying and visualizing connectivity at the whole-brain scale. By integrating data from recent large-scale EM reconstructions (presented in companion studies), FishExplorer enables researchers to validate circuit models, explore wiring principles, and generate new hypotheses. As a continuously evolving resource, FishExplorer is designed to facilitate collaborative discovery and serve the growing needs of the teleost neuroscience community.

neuroscience↗

bioRxiv2025

A connectomic resource for neural cataloguing and circuit dissection of the larval zebrafish brain

We present a correlated light and electron microscopy (CLEM) dataset from a 7-day-old larval zebrafish, integrating confocal imaging of genetically labeled excitatory (vglut2a) and inhibitory (gad1b) neurons with nanometer-resolution serial section EM. The dataset spans the brain and anterior spinal cord, capturing >180,000 segmented soma, >40,000 molecularly annotated neurons, and 30 million synapses, most of which were classified as excitatory, inhibitory, or modulatory. To characterize the directional flow of activity across the brain, we leverage the synaptic and cell body annotations to compute region-wise input and output drive indices at single cell resolution. We illustrate the datasets utility by dissecting and validating circuits in three distinct systems: water flow direction encoding in the lateral line, recurrent excitation and contralateral inhibition in a hindbrain motion integrator, and functionally relevant targeted long-range projections from a tegmental excitatory nucleus, demonstrating that this resource enables rigorous hypothesis testing as well as exploratory-driven circuit analysis. The dataset is integrated into an open-access platform optimized to facilitate community reconstruction and discovery efforts throughout the larval zebrafish brain.

neuroscience↗

bioRxiv2025

A Spinal Circuit for Hypoxia-Evoked Motor Output in Zebrafish Larvae

Oxygen availability is a critical environmental variable that shapes animal physiology and behavior. In larval zebrafish, acute hypoxia elicits a distinct increase in rhythmic pectoral fin movements, a behavior thought to facilitate oxygen uptake. While peripheral oxygen sensors such as neuroepithelial cells (NECs) and Merkel-like cells (MLCs) have been well characterized, the motor circuits responsible for executing this behavior remain unknown. Four distinct lower motor nerve branches in the spinal cord have been shown to innervate the pectoral fin muscles and are candidate effectors of hypoxia-induced behaviors. Here, we identify the neural pathways that transform hypoxia detection into a dedicated motor output. Using high-speed behavioral tracking, we confirm that hypoxia reliably increases pectoral fin beat frequency without affecting locomotor tail activity or visually guided swimming. Two-photon calcium imaging in Tg(ChaTa:Gal4;UAS:GCaMP6s) larvae reveals that a subset of cholinergic spinal motor neurons is selectively active during hypoxia-induced fin movements. Targeted laser ablation of pectoral fin motor nerves abolishes the response, demonstrating the necessity of descending input for this behavior. Our findings define a distributed, partially redundant motor circuit that implements a homeostatic fin response to hypoxia. By establishing a mechanistic framework for this behavior in a genetically accessible vertebrate model, this work enables future studies of oxygen sensing, sensorimotor integration, and the neural basis of homeostatic motor control.

neuroscience↗

bioRxiv2025

Cardiac interoception impacts behavior and brain-wide neuronal dynamics

We sought to explore the question as to whether an animals behavior can be modified by internal physiological changes. We focused on the optomotor response, in which an animal moves in response to visual gratings, because it is quantitative, robust, and evolutionarily conserved. Using larval zebrafish, we demonstrate that engagement in the optomotor response is inversely related to heart rate. We modulate heart rate by external threat, activation or blockade of the sympathetic nervous system, pharmacological blockade of the cardiac pacemaker channel, and direct optogenetic pacing of the heart, and find that the correlation persists through all perturbations. We find neurons in the primary sensory ganglia and several regions of the brain whose activity reflects changes in heart rate, some more active during bradycardia and some during tachycardia. Specifically, we show that the area postrema, known to be a center of cardiovascular integration, shows particularly strong encoding of heart rate, both following threat and during optogenetic cardiac pacing. We suggest that there may be neural mechanisms to assess heart rate changes over time, and that this interoceptive measurement is used to regulate other neural circuits and behavioral output.

neuroscience↗

bioRxiv2024

Sleep Disruption Improves Performance in Simple Olfactory and Visual Decision-Making Tasks

Sleep disruption drastically impacts cognitive functions including decision-making and attention across many different species. In this study, we leveraged the small size and conserved vertebrate brain structure of larval zebrafish to investigate how sleep disruption modulates visual-and olfactory-decision-making. Strikingly, sleep disruption improved performance in both paradigms. Specifically, sleep disruption lengthens reaction times and increases correct decisions in a visual motion discrimination task, an effect that we attribute to longer integration periods in disrupted animals. Using a drift diffusion model, we predict specific circuit changes underlying these effects. Additionally, we demonstrate that sleep disruption heightens odor sensitivity in an olfactory decision-making task, likely mediated by cortisol. Our findings lay essential groundwork for investigating the brain circuit changes that arise from sleep disruption across species.

neuroscience↗

bioRxiv2023

Peripheral detection of viruses shapes brain immunity and behavior in zebrafish

Olfactory sensory neurons (OSNs) are constantly exposed to pathogens, including viruses. However, serious brain infection via the olfactory route rarely occurs. When OSNs detect a virus, they coordinate local antiviral immune responses to stop virus progression to the brain. Despite effective immune control in the olfactory periphery, pathogen-triggered neuronal signals reach the CNS via the olfactory bulb (OB). We hypothesized that neuronal detection of a virus by OSNs initiates neuroimmune responses in the OB that prevent pathogen invasion. Using zebrafish (Danio rerio) as a model, we demonstrate viral-specific neuronal activation of OSNs projecting into the OB, indicating that OSNs are electrically activated by viruses. Further, behavioral changes are seen in both adult and larval zebrafish after viral exposure. By profiling the transcription of single cells in the OB after OSNs are exposed to virus, we found that both microglia and neurons enter a protective state. Microglia and macrophage populations in the OB respond within minutes of nasal viral delivery followed decreased expression of neuronal differentiation factors and enrichment of genes in the neuropeptide signaling pathway in neuronal clusters. Pituitary adenylate-cyclase-activating polypeptide (pacap), a known antimicrobial, was especially enriched in a neuronal cluster. We confirm that PACAP is antiviral in vitro and that PACAP expression increases in the OB 1 day post-viral treatment. Our work reveals how encounters with viruses in the olfactory periphery shape the vertebrate brain by inducing antimicrobial programs in neurons and by altering host behavior.

immunology↗

bioRxiv2020

Larval zebrafish use olfactory detection of sodium and chloride to avoid salt-water

Salinity levels constrain the habitable environment of all aquatic organisms. Zebrafish are freshwater fish that cannot tolerate high salt environments and would, therefore, benefit from neural mechanisms that enable the navigation of salt gradients to avoid high salinity. Yet, zebrafish lack epithelial sodium channels, the primary conduit land animals use to taste sodium. This suggests fish may possess novel, undescribed mechanisms for salt detection. In the present study, we show that zebrafish, indeed, respond to small temporal increases in salt by reorienting more frequently. Further, we use calcium imaging techniques to identify the olfactory system as the primary sense used for salt detection, and we find that a specific subset of olfactory receptor neurons encodes absolute salinity concentrations by detecting monovalent anions and cations. In summary, our study establishes that zebrafish larvae have the ability to navigate, and thus detect salinity gradients, and that this is achieved through previously undescribed sensory mechanisms for salt detection.

neuroscience↗

bioRxiv2020

Navigational strategies underlying temporal phototaxis in Drosophila larvae

Navigating across light gradients is essential for survival for many animals. However, we still have a poor understanding of the algorithms that underlie such behaviors. Here we develop a novel phototaxis assay for Drosophila larvae in which light intensity is always spatially uniform but updates depending on the location of the animal in the arena. Even though larvae can only rely on temporal cues in this closed-loop setup, we find that they are capable of finding preferred areas of low light intensity. Further detailed analysis of their behavior reveals that larvae turn more frequently and that heading angle changes increase when they experience brightness increments over extended periods of time. We suggest that temporal integration of brightness change during runs is an important - and so far largely unexplored - element of phototaxis. Summary statementUsing a novel closed-loop behavioral assay, we show that Drosophila larvae can navigate light gradients exclusively using temporal cues. Analyzing and modeling their behavior in detail, we propose that larvae achieve this by integrating brightness change during runs.

animal behavior and cognition↗

bioRxiv2019

Probabilistic Models of Larval Zebrafish Behavior: Structure on Many Scales

Nervous systems have evolved to combine environmental information with internal state to select and generate adaptive behavioral sequences. To better understand these computations and their implementation in neural circuits, natural behavior must be carefully measured and quantified. Here, we collect high spatial resolution video of single zebrafish larvae swimming in a naturalistic environment and develop models of their action selection across exploration and hunting. Zebrafish larvae swim in punctuated bouts separated by longer periods of rest called interbout intervals. We take advantage of this structure by categorizing bouts into discrete types and representing their behavior as labeled sequences of bout-types emitted over time. We then construct probabilistic models - specifically, marked renewal processes - to evaluate how bout-types and interbout intervals are selected by the fish as a function of its internal hunger state, behavioral history, and the locations and properties of nearby prey. Finally, we evaluate the models by their predictive likelihood and their ability to generate realistic trajectories of virtual fish swimming through simulated environments. Our simulations capture multiple timescales of structure in larval zebrafish behavior and expose many ways in which hunger state influences their action selection to promote food seeking during hunger and safety during satiety.

animal behavior and cognition↗