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The zebrafish visual system has become a paradigmatic preparation for behavioral and systems neuroscience. Around 40 types of retinal ganglion cells (RGCs) serve as matched filters for stimulus features, including light, optic flow, prey, and objects on a collision course. RGCs distribute their signals via axon collaterals to 12 retinorecipient areas in forebrain and midbrain. The major visuomotor hub, the optic tectum, harbors nine RGC input layers that combine information on multiple features. The retinotopic map in the tectum is locally adapted to visual scene statistics and visual subfield-specific behavioral demands. Tectal projections to premotor centers are topographically organized according to behavioral commands. The known connectivity in more than 20 processing streams allows us to dissect the cellular basis of elementary perceptual and cognitive functions. Visually evoked responses, such as prey capture or loom avoidance, are controlled by dedicated multistation pathways that-at least in the larva-resemble labeled lines. This architecture serves the neuronal code's purpose of driving adaptive behavior.

The superior colliculus, or tectum in the case of non-mammalian vertebrates, is a part of the brain that registers events in the surrounding space, often through vision and hearing, but also through electrosensation, infrared detection, and other sensory modalities in diverse vertebrate lineages. This information is used to form maps of the surrounding space and the positions of different salient stimuli in relation to the individual. The sensory maps are arranged in layers with visual input in the uppermost layer, other senses in deeper positions, and a spatially aligned motor map in the deepest layer. Here, we will review the organization and intrinsic function of the tectum/superior colliculus and the information that is processed within tectal circuits. We will also discuss tectal/superior colliculus outputs that are conveyed directly to downstream motor circuits or via the thalamus to cortical areas to control various aspects of behavior. The tectum/superior colliculus is evolutionarily conserved among all vertebrates, but tailored to the sensory specialties of each lineage, and its roles have shifted with the emergence of the cerebral cortex in mammals. We will illustrate both the conserved and divergent properties of the tectum/superior colliculus through vertebrate evolution by comparing tectal processing in lampreys belonging to the oldest group of extant vertebrates, larval zebrafish, rodents, and other vertebrates including primates., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Looming visual stimuli result in escape responses that are conserved from insects to humans. Despite their importance for survival, the circuits mediating visual startle have only recently been explored in vertebrates. Here we show that the zebrafish thalamus is a luminance detector critical to visual escape. Thalamic projection neurons deliver dim-specific information to the optic tectum, and ablations of these projections disrupt normal tectal responses to looms. Without this information, larvae are less likely to escape from dark looming stimuli and lose the ability to escape away from the source of the loom. Remarkably, when paired with an isoluminant loom stimulus to the opposite eye, dimming is sufficient to increase startle probability and to reverse the direction of the escape so that it is toward the loom. We suggest that bilateral comparisons of luminance, relayed from the thalamus to the tectum, facilitate escape responses and are essential for their directionality., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Spontaneous patterns of activity in the developing visual system may play an important role in shaping the brain for function. During the period 4-9 dpf (days post-fertilization), larval zebrafish learn to hunt prey, a behavior that is critically dependent on the optic tectum. However, how spontaneous activity develops in the tectum over this period and the effect of visual experience are unknown. Here we performed two-photon calcium imaging of GCaMP6s zebrafish larvae at all days from 4 to 9 dpf. Using recently developed graph theoretic techniques, we found significant changes in both single-cell and population activity characteristics over development. In particular, we identified days 5-6 as a critical moment in the reorganization of the underlying functional network. Altering visual experience early in development altered the statistics of tectal activity, and dark rearing also caused a long-lasting deficit in the ability to capture prey. Thus, tectal development is shaped by both intrinsic factors and visual experience., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Unlabelled: Topographic maps are common throughout the nervous system, yet their functional role is still unclear. In particular, whether they are necessary for decoding sensory stimuli is unknown. Here we examined this question by recording population activity at the cellular level from the larval zebrafish tectum in response to visual stimuli at three closely spaced locations in the visual field. Due to map imprecision, nearby stimulus locations produced intermingled tectal responses, and decoding based on map topography yielded an accuracy of only 64%. In contrast, maximum likelihood decoding of stimulus location based on the statistics of the evoked activity, while ignoring any information about the locations of neurons in the map, yielded an accuracy close to 100%. A simple computational model of the zebrafish visual system reproduced these results. Although topography is a useful initial decoding strategy, we suggest it may be replaced by better methods following visual experience., Significance Statement: A very common feature of brain wiring is that neighboring points on a sensory surface (eg, the retina) are connected to neighboring points in the brain. It is often assumed that this "topography" of wiring is essential for decoding sensory stimuli. However, here we show in the developing zebrafish that topographic decoding performs very poorly compared with methods that do not rely on topography. This suggests that, although wiring topography could provide a starting point for decoding at a very early stage in development, it may be replaced by more accurate methods as the animal gains experience of the world., (Copyright © 2016 the authors 0270-6474/16/365385-12$15.00/0.)

The tectum has long been known as a hub of visual processing, and recent studies have elucidated many of the circuit-level mechanisms by which tectal neurons filter visual information. Here, we use population-scale imaging of tectal neurons expressing a genetically encoded calcium indicator to characterize tectal responses to non-visual stimuli in zebrafish. We identify ensembles of neurons responsive to stimuli for each of three sensory modalities: vision, audition, and water flow sensation. These ensembles display consistently represented response profiles to our stimuli, and each has a preferred stimulus and salient feature to which it is most responsive. Each sensory modality drives a unique spatial profile of activity in the tectal neuropil, suggesting that the neuropil's laminar structure functionally subserves multiple modalities. The positions of the responsive neurons in the periventricular layer are also distinct across modalities, and very few neurons are responsive to multiple modalities. The cells contributing to each ensemble are highly variable from trial to trial, but ensembles contain "cores" of reliably responsive cells, suggesting a mechanism whereby they could maintain consistency in reporting salient stimulus features while retaining flexibility to report on similar stimuli. Finally, we find that co-presentation of auditory or water flow stimuli suppress visual responses in the tectum., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Branching is an important mechanism by which axons navigate to their targets during neural development. For instance, in the developing zebrafish retinotectal system, selective branching plays a critical role during both initial pathfinding and subsequent arborisation once the target zone has been reached. Here we show how quantitative methods can help extract new information from time-lapse imaging about the nature of the underlying branch dynamics. First, we introduce Dynamic Time Warping to this domain as a method for automatically matching branches between frames, replacing the effort required for manual matching. Second, we model branch dynamics as a birth-death process, i.e. a special case of a continuous-time Markov process. This reveals that the birth rate for branches from zebrafish retinotectal axons, as they navigate across the tectum, increased over time. We observed no significant change in the death rate for branches over this time period. However, blocking neuronal activity with TTX slightly increased the death rate, without a detectable change in the birth rate. Third, we show how the extraction of these rates allows computational simulations of branch dynamics whose statistics closely match the data. Together these results reveal new aspects of the biology of retinotectal pathfinding, and introduce computational techniques which are applicable to the study of axon branching more generally.

The zebrafish retinotectal projection provides an attractive model system for studying many aspects of topographic map formation and maintenance. Visual connections initially start to form between 3 and 5 days postfertilization, and remain plastic throughout the life of the fish. Zebrafish are easily manipulated surgically, genetically, and chemically, and a variety of molecular tools exist to enable visualization and control of various aspects of map development. Here, we review zebrafish retinotectal map formation, focusing particularly on the detailed structure and dynamics of the connections, the molecules that are important in map creation, and how activity regulates the maintenance of the map., (© 2015 Wiley Periodicals, Inc.)

The relative importance of neural activity versus activity-independent cues in shaping the initial wiring of the brain is still largely an open question. While activity is clearly critical for circuit rearrangements after initial connections have been made, whether it also plays a role in initial axon pathfinding remains to be determined. Here, we investigated this question using the guidance of zebrafish retinal ganglion cell axons to their targets in the tectum as a model. Recent results have implicated biased branching as a key feature of pathfinding in the zebrafish tectum. Using tetrodotoxin to silence neural activity globally, we found a decrease in the area covered by axon branches during pathfinding. After reaching the target, there were dynamic differences in axon length, area and the number of branches between conditions. However, other aspects of pathfinding were unaffected by silencing, including the ratio of branches directed toward the target, length, and number of branches, as well as turning angle, velocity, and number of growth cones per axon. These results challenge the hypothesis that neural connections develop in sequential stages of molecularly guided pathfinding and activity-based refinement. Despite a maintenance of overall guidance, axon pathfinding dynamics can nevertheless be altered by activity loss., (© 2015 Wiley Periodicals, Inc.)

The topographic projection from the eye to the tectum (amphibians and fish)/superior colliculus (birds and mammals) is a paradigm model system for studying mechanisms of neural wiring development. It has previously been proposed that retinal ganglion cell axons use distinct guidance strategies in fish vs. mammals, with direct guidance to the tectal target zone in the former and overshoot followed by biased branching toward the target zone in the latter. Here we visualized individual retinal ganglion cell axons as they grew over the tectum in zebrafish for periods of 10-21 hours and analyzed these results using an array of quantitative measures. We found that, although axons were generally guided directly toward their targets, this occurred without growth cone turning. Instead, axons branched dynamically and profusely throughout pathfinding, and successive branches oriented growth cone extension toward a target zone in a stepwise manner. These data suggest that the guidance strategies used between fish and mammals may be less distinct than previously thought., (Copyright © 2012 Wiley Periodicals, Inc.)

The cerebellum is a brain region responsible for motor coordination and for refining motor programs. While a great deal is known about the structure and connectivity of the mammalian cerebellum, fundamental questions regarding its function in behavior remain unanswered. Recently, the zebrafish has emerged as a useful model organism for cerebellar studies, owing in part to the similarity in cerebellar circuits between zebrafish and mammals. While the cell types composing their cerebellar cortical circuits are generally conserved with mammals, zebrafish lack deep cerebellar nuclei, and instead a majority of cerebellar output comes from a single type of neuron: the eurydendroid cell. To describe spatial patterns of cerebellar output in zebrafish, we have used genetic techniques to label and trace eurydendroid cells individually and en masse. We have found that cerebellar output targets the thalamus and optic tectum, and have confirmed the presence of pre-synaptic terminals from eurydendroid cells in these structures using a synaptically targeted GFP. By observing individual eurydendroid cells, we have shown that different medial-lateral regions of the cerebellum have eurydendroid cells projecting to different targets. Finally, we found topographic organization in the connectivity between the cerebellum and the optic tectum, where more medial eurydendroid cells project to the rostral tectum while lateral cells project to the caudal tectum. These findings indicate that there is spatial logic underpinning cerebellar output in zebrafish with likely implications for cerebellar function.

The visual pathway is tasked with processing incoming signals from the retina and converting this information into adaptive behavior. Recent studies of the larval zebrafish tectum have begun to clarify how the 'micro-circuitry' of this highly organized midbrain structure filters visual input, which arrives in the superficial layers and directs motor output through efferent projections from its deep layers. The new emphasis has been on the specific function of neuronal cell types, which can now be reproducibly labeled, imaged and manipulated using genetic and optical techniques. Here, we discuss recent advances and emerging experimental approaches for studying tectal circuits as models for visual processing and sensorimotor transformation by the vertebrate brain.