Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May 19;35(10):2457-2466.e4.
doi: 10.1016/j.cub.2025.04.027. Epub 2025 May 2.

Neural circuits underlying divergent visuomotor strategies of zebrafish and Danionella cerebrum

Kaitlyn E Fouke  1 , Zichen He  2 , Matthew D Loring  1 , Eva A Naumann  3
Affiliations

Neural circuits underlying divergent visuomotor strategies of zebrafish and Danionella cerebrum

Kaitlyn E Fouke et al. Curr Biol. .

Abstract

Many animals respond to sensory cues with species-specific coordinated movements.1,2 A universal visually guided behavior is the optomotor response (OMR),3,4,5,6 which stabilizes the body by following optic flow induced by displacements in currents.7 While the brain-wide OMR circuits in zebrafish (Danio rerio) have been characterized,8,9,10,11,12 the homologous neural functions across teleost species with different ecological niches, such as Danionella cerebrum,13,14,15 remain largely unexplored. Here, we directly compare larval zebrafish and D. cerebrum to uncover the neural mechanisms underlying the natural variation of visuomotor coordination. Closed-loop behavioral tracking during visual stimulation revealed that D. cerebrum follow optic flow by swimming continuously, punctuated with sharp directional turns, in contrast to the burst-and-glide locomotion of zebrafish.16 Although D. cerebrum swim at higher average speeds, they lack the direction-dependent velocity modulation observed in zebrafish. Two-photon calcium imaging and tail tracking showed that both species exhibit direction-selective encoding in putative homologous regions, with D. cerebrum containing more monocular neurons. D. cerebrum sustain significantly longer directed swims across all stimuli than zebrafish, with zebrafish reducing tail movement duration in response to oblique, turn-inducing stimuli. While locomotion-associated neurons in D. cerebrum display more prolonged activity than zebrafish, lateralized turn-associated neural activity in the hindbrain suggests a shared neural circuit architecture that independently controls movement vigor and direction. These findings highlight the diversity in visuomotor strategies among teleost species with shared circuit motifs, establishing a framework for unraveling the neural mechanisms driving continuous and discrete locomotion.

Keywords: Danionella cerebrum; calcium imaging; comparative neurophysiology; locomotor behavior; visuomotor transformation; zebrafish.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Figures

Figure 1.
Figure 1.. Freely swimming DC perform OMR with smooth, continuous swims, punctuated with sharp turns.
A Closed-loop behavioral assay to test global motion cues in freely swimming fish. Heading direction (Δν) and position (Δx, Δy) are extracted to lock the stimulus to the body axis. B Zebrafish (ZF, 7 days post fertilization (dpf)), Danionella cerebrum (DC, 8 dpf). C Cumulative distance and velocity of representative trials for ZF and DC to forward motion (green). ZF move in bouts, while DC swim faster and continuously. D Median velocity box plots show that ZF exhibit direction-dependent velocity modulation. DC swims at a statistically higher velocity than ZF for oblique stimuli (N = ZF: 26, DC: 12 fish; * p < 0.05, two-way ANOVA, Tukey post hoc), indicating lack of modulating velocity. E Cumulative heading direction change to rightward (red) and leftward motion (blue) of representative trials for ZF and DC. Zoom in: sharp orientation changes (arrowheads) were observed in both species. F Instantaneous angular acceleration for data in E. ZF generates many sharp turns, DC move in ballistic, straight swims with occasional directed, high-angle turns (arrowheads). G Median angular velocity shows that both species follow the direction of optic flow, with positive and negative angular velocity indicating rightward and leftward turning, respectively (* p < 0.05, two-way ANOVA, Tukey post hoc). H Instantaneous angular acceleration for ZF and DC. Logarithmic distributions highlight differences in movement modes. High values indicate sharp, burst-like turns, while lower values occur during continuous, smooth turns (> 10 °/s2) or gliding. Center white lines indicate median, dashed lines quartiles. All ZF and DC angular accelerations differ significantly (* p < 0.05, Kruskal-Wallis test with Bonferroni correction). See also Video S1 and Figure S1.
Figure 2.
Figure 2.. Larval DC and ZF share visual motion processing neural architecture.
A Imaging setup for volumetric two-photon imaging of tail-freed larval fish during visual stimulation. B Average dF/F of representative ZF and DC neurons, associated rose plots, color-coded for direction selectivity. C Median frequency polar histograms of motion-responsive neurons with weighted mean dF/F ≥ 0.2 in representative fish (N = ZF: 2931, DC: 818 neurons), with the angle representing the direction selectivity index (DSI). D Whole-brain distribution of visually responsive neurons for data in C. Each dot represents a neural source, its hue indicates direction selectivity (≥ 0.2 mean dF/F), otherwise grey, plotted on greyscale GCaMP anatomy. Putatively homologous pretectum (Pt, Pt’) and anterior hindbrain (aHB, aHB’) regions in ZF (white lines) and DC (white dashed lines, derived from mapzebrain, STAR Methods) contain lateralized direction-selective neurons. Heatmaps show trial averaged dF/F, sorted into 28 shared functional clusters. E Rose plots for indicated clusters across all fish. F Proportion of direction-selective neurons in indicated functional clusters (N = ZF: 5, DC: 5 fish; * p < 0.05, two-way ANOVA, Tukey post hoc). G Average DSI is similar in ZF and DC (ZF = 0.62, DC = 0.66; p > 0.05, Student’s t-test; N = ZF: 5, DC: 5 fish). H ZF tended to show an elevated proportion of motion-responsive neurons compared to DC (ZF = 0.13, DC = 0.06; p = 0.059, Student’s t-test; N = ZF: 5, DC: 5 fish). I Binocularity index (BI) maps for representative ZF and DC. J Histogram of BI distribution of all motion-responsive neurons (N = ZF: 55272, DC: 35780 neurons). K DC show a higher proportion of purely monocular neurons (ZF = 0.16, DC = 0.37; * p < 0.05, Student’s t-test; N = ZF: 5, DC: 5 fish) than ZF. L BI ratios show a higher fraction of binocular neurons in ZF compared to DC (ZF = 0.72, DC = 0.24; p = 0.010, Student’s t-test; N = ZF: 5, DC: 5 fish). See also Video S2 and Figure S2, S3.
Figure 3.
Figure 3.. Head-fixed larval DC exhibit longer visually evoked swim events than ZF.
A Schematic of tail tracking in head-fixed fish during imaging. The tail angle (Θ) is the sum of all segment angles. Positive and negative Θ indicate right and left tail movements. B Representative ZF and DC swims evoked by visual motion (color and arrows show stimulus direction). Black traces represent tail angles during detected events, otherwise grey. Arrowheads highlight large tail flicks in DC. Bar graphs show the mean tail angle across each event. C Mean angle and duration for all visually evoked swims in head-embedded ZF (N = 4 fish, 1887 swims); DC (N = 3 fish, 331 swims). Bars represent swims evoked during eight visual stimuli (colored for direction), with its direction indicating mean tail angle, its length mean swim duration. In ZF, swims during forward last significantly longer than those during turn-inducing stimuli (**** p < 0.0001, two-way ANOVA followed by within-species one-way ANOVA). DC swims are less lateralized, with no significant shortening for oblique stimuli. D Mean tail angle across all swims for ZF and DC, white lines indicate medians. Both DC and ZF match optic flow direction, with ZF exhibiting higher angle turning than DC during turn-inducing stimuli (* p < 0.05, two-way ANOVA, Tukey post hoc). E Violin plots with medians (white lines) of all swim durations for ZF (N = 4 fish, 3568 events) and DC (N = 3 fish, 855 events) plotted on a log scale. DC performed significantly longer swims than ZF (DC = 0.75 s, ZF = 0.29 s; **** p < 0.0001, two-way ANOVA main effect). F Distribution of all swim durations; white lines indicate medians. DC show significantly longer swims than ZF across most directions (* p < 0.05, two-way ANOVA, Tukey post hoc). See also Video S2 and Figure S4.
Figure 4.
Figure 4.. Medial hindbrain neurons encode turning behaviors in both species.
A Schematic of the bidirectional decoding approach to identify motor-associated neurons based on the temporal alignment of calcium signal increases with swims, quantifying each neuron’s motor decoding accuracy. Right, idealized illustrations of motor-associated, non-motor-associated neurons, and specific motor event-associated neurons. B Top, tail traces in representative swim events. Bottom, dF/F of top motor-associated neurons during representative swims for ZF and DC. Green shading denotes movement duration. C Anatomical distribution of motor decoding accuracy in representative DC and ZF brain volumes, highlighting enrichment of motor-associated neurons (dark green) in registered hindbrain and nMLF regions. D Top 20 % motor-associated neurons are not responsive to visual stimuli (N = ZF: 4, DC: 2 fish; n = ZF: 14063, DC: 5790 neurons). Top, aligned swims (green); middle, average dF/F aligned to the start of all swims; bottom, average dF/F aligned to visual motion onset. E Average dF/F for all swim onset associated neurons, color-coded for duration. DC neurons display elongated activity compared to ZF (N = ZF: 4, DC: 2 fish; n = ZF: 5802, DC: 1659 neurons). F Top, DC motor-associated neurons show elongated ‘ON’ duration compared to ZF. Bottom, non-motor associated neurons in DC and ZF show similar ‘ON’ duration (N = ZF: 4, DC: 2 fish; * p <0.05, two-way ANOVA, Tukey post-hoc). G Top 20% of motor-associated neurons during representative turns are selective for either left or right turns or are active during both. H Distribution of top 20% motor-associated neurons color-coded for turn direction in representative ZF and DC brains. Inset: neurons in putatively homologous vSPNs from all fish exhibit strongly lateralized activity, color-coded by its motor direction index, i.e., neurons on the anatomical left respond more during left turns and vice versa (N = ZF: 4 fish, 531 neurons; DC: 2 fish, 128 neurons). I Motor-associated neurons putative vSPNs correlate more with ipsilateral turn motor regressors. Boxplots represent Pearson’s correlation coefficients for motor-associated neurons in the anatomically registered vSPNs (N = ZF: 4, DC: 2 fish; n = ZF: 531, DC: 128 neurons, ** p < 0.01, two-way ANOVA, Tukey post-hoc). See also Video S2 and Figure S5, 6.
See this image and copyright information in PMC

Update of

References

    1. Bouvier J, Caggiano V, Leiras R, Caldeira V, Bellardita C, Balueva K, Fuchs A, and Kiehn O (2015). Descending Command Neurons in the Brainstem that Halt Locomotion. Cell 163, 1191–1203. 10.1016/j.cell.2015.10.074. - DOI - PMC - PubMed
    1. Churchland MM, Cunningham JP, Kaufman MT, Foster JD, Nuyujukian P, Ryu SI, and Shenoy KV (2012). Neural population dynamics during reaching. Nature 487, 51–56. 10.1038/nature11129. - DOI - PMC - PubMed
    1. Oteiza P, Odstrcil I, Lauder G, Portugues R, and Engert F (2017). A novel mechanism for mechanosensory-based rheotaxis in larval zebrafish. Nature 547, 445–448. 10.1038/nature23014. - DOI - PMC - PubMed
    1. Winship IR, Crowder NA, and Wylie DRW (2006). Quantitative Reassessment of Speed Tuning in the Accessory Optic System and Pretectum of Pigeons. Journal of Neurophysiology 95, 546–551. 10.1152/jn.00921.2005. - DOI - PubMed
    1. Masseck OA, and Hoffmann K-P (2009). Question of Reference Frames: Visual Direction-Selective Neurons in the Accessory Optic System of Goldfish. Journal of Neurophysiology 102, 2781–2789. 10.1152/jn.00415.2009. - DOI - PubMed

LinkOut - more resources