Final Report Summary - ZEBRAFISH PERCEPTION (Sensory perception: neural representation and modulation)
1.Sustained rhythmic brain activity underlies visual motion perception in zebrafish
Following coherently moving visual stimuli (conditioning stimulus, CS) many organisms perceive, in the absence of physical stimuli, illusory motion in the opposite direction, a phenomenon known as the motion aftereffect (MAE). Here we use MAE as a tool to study the neuronal basis of visual motion perception in zebrafish larvae.
Using the zebrafish optokinetic response as an indicator of visual motion perception, we showed that larvae perceive MAE. Blocking eye movements using optogenetics during CS did not prevent the emergence of MAE, yet, tectal ablation significantly weakened it. Using two-photon calcium imaging of behaving GCaMP3 larvae we found post-stimulation sustained rhythmic activity among direction-selective tectal neurons that was associated with the perception of MAE. Additionally, tectal neurons tuned to the CS direction habituated, but neurons in the retina did not. Finally, a model based on competition between direction-selective neurons reproduced MAE, suggesting a neuronal circuit capable of generating perception of visual motion.
2. Ongoing spontaneous activity in a visual region of zebrafish brain
Spontaneous neuronal activity is spatiotemporally structured, influencing brain computations. Nevertheless, the neuronal interactions underlying these spontaneous activity patterns, and their biological relevance, remain elusive. Here, we addressed these questions using two-photon calcium imaging of intact zebrafish larvae to monitor the neuron-to-neuron spontaneous activity fine structure in the tectum, a region involved in visual spatial detection. Spontaneous activity was organized in topographically compact assemblies, grouping functionally similar neurons rather than merely neighboring ones, reflecting the tectal retinotopic map despite being independent of retinal drive. Assemblies represent all-or-none-like sub-networks shaped by competitive dynamics, mechanisms advantageous for visual detection in noisy natural environments. Notably, assemblies were tuned to the same angular sizes and spatial positions as prey-detection performance in behavioral assays, and their spontaneous activation predicted directional tail movements.
Moreover, we studied the emergence and development of this activity and the influence of retinal inputs on the maturation of tectal spatiotemporal structure remain uncharacterized. We found that in the absence of retinal inputs, the optic tectum was still capable of developing a spatial structure associated with the circuit's functional roles, and predictive of behavior. We conclude that neither visual experience nor intrinsic retinal activity are essential for the emergence of a functionally relevant spatial structure.
Using light-sheet microscopy we are now studying the spontaneous activity patterns and mechanisms that enable the generation of self-generated behaviors.
So far, we observed that specific brain regions in the dorsal hindbrain predict the onset of a self-generated tail movement, and that other brain regions in the mid- and hindbrain show transient states predictive of the direction of a potential self-generated tail movement. We thus suggest that the antisymmetric fluctuations determine the direction of an impeding self-generated movement (turning left or right). A second signal predictive of the onset of the movement (the when) could gate the generation of the movement. Although the when and what signals could be independent, they have to happen at the same time in order to induce a self-generated behaviour.
3. Gustatory perception in the zebrafish brain
Zebrafish larva is a unique model for whole-brain functional imaging and to study sensory-motor integration in the vertebrate brain. To take full advantage of this system, one needs to design sensory environments that can mimic the complex spatiotemporal stimulus patterns experienced by the animal in natural conditions. We report on a novel open-ended microfluidic device that delivers pulses of chemical stimuli to agarose-restrained larvae with near-millisecond switching rate and unprecedented spatial and concentration accuracy and reproducibility. In combination with two- photon calcium imaging and recordings of tail movements, we found that stimuli of opposite hedonic values induced different circuit activity patterns. Moreover, by precisely controlling the duration of the stimulus (50–500 ms), we found that the probability of generating a gustatory-induced behavior is encoded by the number of neurons activated. This device may open new ways to dissect the neural- circuit principles underlying chemosensory perception.
Following coherently moving visual stimuli (conditioning stimulus, CS) many organisms perceive, in the absence of physical stimuli, illusory motion in the opposite direction, a phenomenon known as the motion aftereffect (MAE). Here we use MAE as a tool to study the neuronal basis of visual motion perception in zebrafish larvae.
Using the zebrafish optokinetic response as an indicator of visual motion perception, we showed that larvae perceive MAE. Blocking eye movements using optogenetics during CS did not prevent the emergence of MAE, yet, tectal ablation significantly weakened it. Using two-photon calcium imaging of behaving GCaMP3 larvae we found post-stimulation sustained rhythmic activity among direction-selective tectal neurons that was associated with the perception of MAE. Additionally, tectal neurons tuned to the CS direction habituated, but neurons in the retina did not. Finally, a model based on competition between direction-selective neurons reproduced MAE, suggesting a neuronal circuit capable of generating perception of visual motion.
2. Ongoing spontaneous activity in a visual region of zebrafish brain
Spontaneous neuronal activity is spatiotemporally structured, influencing brain computations. Nevertheless, the neuronal interactions underlying these spontaneous activity patterns, and their biological relevance, remain elusive. Here, we addressed these questions using two-photon calcium imaging of intact zebrafish larvae to monitor the neuron-to-neuron spontaneous activity fine structure in the tectum, a region involved in visual spatial detection. Spontaneous activity was organized in topographically compact assemblies, grouping functionally similar neurons rather than merely neighboring ones, reflecting the tectal retinotopic map despite being independent of retinal drive. Assemblies represent all-or-none-like sub-networks shaped by competitive dynamics, mechanisms advantageous for visual detection in noisy natural environments. Notably, assemblies were tuned to the same angular sizes and spatial positions as prey-detection performance in behavioral assays, and their spontaneous activation predicted directional tail movements.
Moreover, we studied the emergence and development of this activity and the influence of retinal inputs on the maturation of tectal spatiotemporal structure remain uncharacterized. We found that in the absence of retinal inputs, the optic tectum was still capable of developing a spatial structure associated with the circuit's functional roles, and predictive of behavior. We conclude that neither visual experience nor intrinsic retinal activity are essential for the emergence of a functionally relevant spatial structure.
Using light-sheet microscopy we are now studying the spontaneous activity patterns and mechanisms that enable the generation of self-generated behaviors.
So far, we observed that specific brain regions in the dorsal hindbrain predict the onset of a self-generated tail movement, and that other brain regions in the mid- and hindbrain show transient states predictive of the direction of a potential self-generated tail movement. We thus suggest that the antisymmetric fluctuations determine the direction of an impeding self-generated movement (turning left or right). A second signal predictive of the onset of the movement (the when) could gate the generation of the movement. Although the when and what signals could be independent, they have to happen at the same time in order to induce a self-generated behaviour.
3. Gustatory perception in the zebrafish brain
Zebrafish larva is a unique model for whole-brain functional imaging and to study sensory-motor integration in the vertebrate brain. To take full advantage of this system, one needs to design sensory environments that can mimic the complex spatiotemporal stimulus patterns experienced by the animal in natural conditions. We report on a novel open-ended microfluidic device that delivers pulses of chemical stimuli to agarose-restrained larvae with near-millisecond switching rate and unprecedented spatial and concentration accuracy and reproducibility. In combination with two- photon calcium imaging and recordings of tail movements, we found that stimuli of opposite hedonic values induced different circuit activity patterns. Moreover, by precisely controlling the duration of the stimulus (50–500 ms), we found that the probability of generating a gustatory-induced behavior is encoded by the number of neurons activated. This device may open new ways to dissect the neural- circuit principles underlying chemosensory perception.