Biology subjects

Loring, M. D.

Publications and source records attributed to Loring, M. D..

4 recordsLinked to original sources

bioRxiv2024

Artificial Embodied Circuits Uncover Neural Architectures of Vertebrate Visuomotor Behaviors

All brains evolve within specific sensory and physical environments1. Traditionally, neuroscience has focused on studying neural circuits in isolation, yet holistic characterization of their function requires integrative brain-body testing2,3. To investigate the neural and biomechanical mechanisms of sensorimotor transformations, we constructed realistic neuromechanical simulations (simZFish) of the larval zebrafish optomotor response, a visual stabilization behavior4,5. By computationally reproducing the body, physical body-water interactions, visual environments, and experimentally derived neural architectures, we closely replicated the behavior of real zebrafish6. Through systematic manipulation of physiological and circuit features, impossible in biological experiments, we demonstrate how embodiment shapes neural circuit architecture and behavior. When challenged with novel visual stimuli, simZFish predicted neuronal response types, which we identified via calcium imaging in the brain of real zebrafish and used to update the simZFish neural network. In virtual rivers, simZFish performed rheotaxis by using current-induced optic flow as navigational cues, compensating for the simulated water flow. Finally, a physical robot (ZBot) validated the role of embodied sensorimotor circuits in maintaining position in a real river with complex fluid dynamics and visual environments. Together, by iterating between simulations, behavioral observations, neural imaging, and robotic testing, we demonstrate the power of an integrative approach to investigating sensorimotor processing. Research HighlightsO_LIDeveloped simZFish, an open-source neuromechanical simulation modeling the zebrafish optomotor response (OMR). C_LIO_LIDemonstrated that simZFish visuomotor neural circuits are sufficient to maintain position in virtual water currents without additional sensory modalities. C_LIO_LIInvestigated how variations in eye geometry influence neural circuit functionality and behavior. C_LIO_LIConducted optic flow analysis of simulated visual input to identify retinal connectivity requirements, uncovering the factors that shape pretectal neurons preference for the lower posterior visual field. C_LIO_LIsimZFish predicted new neural response types confirmed via real zebrafish calcium imaging. C_LIO_LIValidated simZFish circuits with a physical robot, ZBot, performing rheotaxis in a natural river with rich visual and complex flow dynamics compared to idealized lab and simulation experiments. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/629427v1_ufig1.gif" ALT="Figure 1"> View larger version (63K): org.highwire.dtl.DTLVardef@11f2acforg.highwire.dtl.DTLVardef@133b1f3org.highwire.dtl.DTLVardef@e808bcorg.highwire.dtl.DTLVardef@1959616_HPS_FORMAT_FIGEXP M_FIG C_FIG Graphical abstractCombining data-driven neuromechanical simulations and robotic testing, we established an integrative framework for investigating embodied neural circuit functions. Leveraging the behavioral, neurobiological, and theoretical foundations of the visually guided optomotor response in larval zebrafish (blue, left), we developed a virtual zebrafish, simZFish (red, middle), to replicate realistic hydrodynamic, anatomical, sensory, neural, and behavioral aspects, permitting the investigation of emergent properties driven by embodiment. Validating these findings using a physical, zebrafish-inspired robot, ZBot (grey, right), in naturalistic environments informs further experiments, hypotheses, and robotic design.

neuroscience↗

bioRxiv2024

Divergent Visuomotor Strategies in Teleosts: Neural Circuit Mechanisms in Zebrafish and Danionella cerebrum

Many animals respond to sensory cues with species-specific coordinated movements to successfully navigate their environment. However, the neural mechanisms that support diverse sensorimotor transformations across species with distinct navigational strategies remain largely unexplored. By comparing related teleost species, zebrafish (Danio rerio, ZF) and Danionella cerebrum (DC), we investigated behavioral patterns and neural architectures during the visually guided optomotor response (OMR). Closed-loop behavioral tracking during visual stimulation revealed that larval ZF employ burst-and-glide locomotion, while larval DC display continuous, smooth swimming punctuated with sharp directional turns. Although DC achieve higher average speeds, they lack the direction-dependent velocity modulation observed in ZF. Whole-brain two-photon calcium imaging and tail tracking in head-fixed fish reveals that both species exhibit direction-selective motion encoding in homologous regions, including the retinorecipient pretectum, with DC exhibiting fewer binocular, direction-selective neurons overall. Kinematic analysis of head-fixed behavior reveals that DC sustain significantly longer directed swim events across all stimuli than ZF, highlighting the divergent visuomotor strategies, with ZF reducing tail movement duration in response to oblique, turn-inducing stimuli. Lateralized motor-associated neural activity in the medial and anterior hindbrain of both species suggests a shared circuit motif, with distinct neural circuits that independently control movement vigor and direction. These findings highlight the diversity in visuomotor strategies among teleost species, underscored by shared sensorimotor neural circuit motifs, and establish a robust framework for unraveling the neural mechanisms driving continuous and discrete visually guided locomotion, paving the way for deeper insights into vertebrate sensorimotor functions. Research HighlightsO_LILarval DC exhibit faster swimming than ZF, matching the direction of visual motion. C_LIO_LIDC execute OMR in smooth, curved swimming patterns, interspersed with sharp directional turns. C_LIO_LIZF and DC share similar visuomotor neural architecture, recruiting pretectal and hindbrain regions. C_LIO_LIZF and DC demonstrate lateralized encoding of turns, particularly in medial hindbrain neurons. C_LI In BriefLarval Danionella cerebrum respond to global visual motion cues in smooth, low-angle swimming patterns, interspersed with sharp directional turns, swimming consistently faster than zebrafish. Fouke et al. use behavioral tracking of freely moving and head fixed fish to reveal an evolutionarily conserved visuomotor neural architecture transforming visual motion cues into species-specific locomotor behaviors. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/624938v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@13076f4org.highwire.dtl.DTLVardef@d18dc8org.highwire.dtl.DTLVardef@1b35025org.highwire.dtl.DTLVardef@152d2f0_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG

neuroscience↗

bioRxiv2021

improv: A flexible software platform for adaptive neuroscience experiments

Current neuroscience research is often limited to testing predetermined hypotheses and post hoc analysis of already collected data. Adaptive experimental designs, in which modeling drives ongoing data collection and selects experimental manipulations, offer a promising alternative. Still, tight integration between models and data collection requires coordinating diverse hardware configurations and complex computations under real-time constraints. Here, we introduce improv, a software platform that allows users to fully integrate custom modeling, analysis, and visualization with data collection and experimental control. We demonstrate both in silico and in vivo how improv enables more efficient experimental designs for discovery and validation across various model organisms and data types. Improv can orchestrate custom real-time behavioral analyses, rapid functional typing of neural responses from large populations via calcium microscopy, and optimal visual stimulus selection. We incorporate real-time machine learning methods for dimension reduction and predictive modeling of latent neural and behavioral features. Finally, we demonstrate how improv can perform model-driven interactive imaging and simultaneous optogenetic photostimulation of visually responsive neurons in the larval zebrafish brain expressing GCaMP6s and the red-shifted opsin rsChRmine. Together, these results demonstrate the power of improv to integrate modeling with data collection and experimental control to achieve next-generation adaptive experiments.

neuroscience↗

bioRxiv2019

Hedgehog signaling regulates neurogenesis in the larval and adult zebrafish hypothalamus

While neurogenesis in the adult hypothalamus is now known to be essential for proper function, the cell-cell signaling events that regulate neurogenesis in this evolutionarily conserved brain region remain poorly understood. Here we show that Hedgehog (Hh)/Gli signaling positively regulates hypothalamic neurogenesis in both larval and adult zebrafish and is necessary and sufficient for normal hypothalamic proliferation rates. Hedgehog-responsive cells are relatively rapidly proliferating pluripotent neural precursors that give rise to dopaminergic, serotonergic, and GABAergic neurons. in situ and transgenic reporter analyses revealed substantial heterogeneity in cell-cell signaling within the hypothalamic niche, with slow cycling Nestin-expressing cells residing among distinct and overlapping populations of Sonic Hh (Shh)-expressing, Hh-responsive, Notch-responsive, and Wnt-responsive radial glia. This work shows for the first time that Hh/Gli-signaling is a key component of the complex cell-cell signaling environment that regulates hypothalamic neurogenesis throughout life.

neuroscience↗