Bahl, Armin
0000-0001-7591-5860 Berufsbeschreibung
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Reflective multi-immersion microscope objectives inspired by the Schmidt telescope
Imaging large, cleared samples requires microscope objectives that combine a large field of view (FOV) with a long working distance (WD) and a high numerical aperture (NA). Ideally, such objectives should be compatible with a wide range of immersion media, which is challenging to achieve with conventional lens-based objective designs. Here we introduce the multi-immersion ‘Schmidt objective’ consisting of a spherical mirror and an aspherical correction plate as a solution to this problem. We demonstrate that a multi-photon variant of the Schmidt objective is compatible with all homogeneous immersion media and achieves an NA of 1.08 at a refractive index of 1.56, 1.1-mm FOV and 11-mm WD. We highlight its versatility by imaging cleared samples in various media ranging from air and water to benzyl alcohol/benzyl benzoate, dibenzyl ether and ethyl cinnamate and by imaging of neuronal activity in larval zebrafish in vivo. In principle, the concept can be extended to any imaging modality, including wide-field, confocal and light-sheet microscopy.
Precise visuomotor transformations underlying collective behavior in larval zebrafish
Complex schooling behaviors result from local interactions among individuals. Yet, how sensory signals from neighbors are analyzed in the visuomotor stream of animals is poorly understood. Here, we studied aggregation behavior in larval zebrafish and found that over development larvae transition from overdispersed groups to tight shoals. Using a virtual reality assay, we characterized the algorithms fish use to transform visual inputs from neighbors into movement decisions. We found that young larvae turn away from virtual neighbors by integrating and averaging retina-wide visual occupancy within each eye, and by using a winner-take-all strategy for binocular integration. As fish mature, their responses expand to include attraction to virtual neighbors, which is based on similar algorithms of visual integration. Using model simulations, we show that the observed algorithms accurately predict group structure over development. These findings allow us to make testable predictions regarding the neuronal circuits underlying collective behavior in zebrafish.
Algorithms underlying flexible phototaxis in larval zebrafish
To thrive, organisms must maintain physiological and environmental variables in suitable ranges. Given that these variables undergo constant fluctuations over varying timescales, how do biological control systems maintain control over these values? We explored this question in the context of phototactic behavior in larval zebrafish. We demonstrate that larval zebrafish use phototaxis to maintain environmental luminance at a set point, that the value of this set point fluctuates on a timescale of seconds when environmental luminance changes, and that it is determined by calculating the mean input across both sides of the visual field. These results expand on previous studies of flexible phototaxis in larval zebrafish; they suggest that larval zebrafish exert homeostatic control over the luminance of their surroundings, and that feedback from the surroundings drives allostatic changes to the luminance set point. As such, we describe a novel behavioral algorithm with which larval zebrafish exert control over a sensory variable.
Visual Projection Neurons Mediating Directed Courtship in Drosophila
Many animals rely on vision to detect, locate, and track moving objects. In Drosophila courtship, males primarily use visual cues to orient toward and follow females and to select the ipsilateral wing for courtship song. Here, we show that the LC10 visual projection neurons convey essential visual information during courtship. Males with LC10 neurons silenced are unable to orient toward or maintain proximity to the female and do not predominantly use the ipsilateral wing when singing. LC10 neurons preferentially respond to small moving objects using an antagonistic motion-based center-surround mechanism. Unilateral activation of LC10 neurons recapitulates the orienting and ipsilateral wing extension normally elicited by females, and the potency with which LC10 induces wing extension is enhanced in a state of courtship arousal controlled by male-specific P1 neurons. These data suggest that LC10 is a major pathway relaying visual input to the courtship circuits in the male brain.
A Visual Interface for Exploring Hypotheses about Neural Circuits
One of the fundamental problems in neurobiological research is to understand how neural circuits generate behaviors in response to sensory stimuli. Elucidating such neural circuits requires anatomical and functional information about the neurons that are active during the processing of the sensory information and generation of the respective response, as well as an identification of the connections between these neurons. With modern imaging techniques, both morphological properties of individual neurons as well as functional information related to sensory processing, information integration and behavior can be obtained. Given the resulting information, neurobiologists are faced with the task of identifying the anatomical structures down to individual neurons that are linked to the studied behavior and the processing of the respective sensory stimuli. Here, we present a novel interactive tool that assists neurobiologists in the aforementioned task by allowing them to extract hypothetical neural circuits constrained by anatomical and functional data. Our approach is based on two types of structural data: brain regions that are anatomically or functionally defined, and morphologies of individual neurons. Both types of structural data are interlinked and augmented with additional information. The presented tool allows the expert user to identify neurons using Boolean queries. The interactive formulation of these queries is supported by linked views, using, among other things, two novel 2D abstractions of neural circuits. The approach was validated in two case studies investigating the neural basis of vision-based behavioral responses in zebrafish larvae. Despite this particular application, we believe that the presented tool will be of general interest for exploring hypotheses about neural circuits in other species, genera and taxa.
Collective behavior emerges from genetically controlled simple behavioral motifs in zebrafish
It is not understood how changes in the genetic makeup of individuals alter the behavior of groups of animals. Here, we find that, even at early larval stages, zebrafish regulate their proximity and alignment with each other. Two simple visual responses, one that measures relative visual field occupancy and one that accounts for global visual motion, suffice to account for the group behavior that emerges. Mutations in genes known to affect social behavior in humans perturb these simple reflexes in individual larval zebrafish and change their emergent collective behaviors in the predicted fashion. Model simulations show that changes in these two responses in individual mutant animals predict well the distinctive collective patterns that emerge in a group. Hence, group behaviors reflect in part genetically defined primitive sensorimotor “motifs,” which are evident even in young larvae.
Neural circuits for evidence accumulation and decision making in larval zebrafish
To make appropriate decisions, animals need to accumulate sensory evidence. Simple integrator models can explain many aspects of such behavior, but how the underlying computations are mechanistically implemented in the brain remains poorly understood. Here we approach this problem by adapting the random-dot motion discrimination paradigm, classically used in primate studies, to larval zebrafish. Using their innate optomotor response as a measure of decision making, we find that larval zebrafish accumulate and remember motion evidence over many seconds and that the behavior is in close agreement with a bounded leaky integrator model. Through the use of brain-wide functional imaging, we identify three neuronal clusters in the anterior hindbrain that are well suited to execute the underlying computations. By relating the dynamics within these structures to individual behavioral choices, we propose a biophysically plausible circuit arrangement in which an evidence integrator competes against a dynamic decision threshold to activate a downstream motor command.
Reflective multi-immersion microscope objectives
We present a novel way of designing multi-immersion microscope objectives inspired by both the mirror-based eyes of scallops and the Schmidt telescope, a wide-field telescope invented in the 1930s. Despite containing only two optical elements and without a correction collar, our design achieves diffraction-limited imaging performance over mm-scale field-of-views in air and in any homogeneous liquid medium. Based on our concept, we built a prototype two-photon microscope objective and demonstrated its versatility by imaging Xenopus tadpoles cleared with BABB (n=1.56) and by imaging the larval Zebrafish brain in vivo in water.
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 developed a novel closed-loop 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 during runs, 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.
A bidirectional network for appetite control in larval zebrafish
Medial and lateral hypothalamic loci are known to suppress and enhance appetite, respectively, but the dynamics and functional significance of their interaction have yet to be explored. Here we report that, in larval zebrafish, primarily serotonergic neurons of the ventromedial caudal hypothalamus (cH) become increasingly active during food deprivation, whereas activity in the lateral hypothalamus (LH) is reduced. Exposure to food sensory and consummatory cues reverses the activity patterns of these two nuclei, consistent with their representation of opposing internal hunger states. Baseline activity is restored as food-deprived animals return to satiety via voracious feeding. The antagonistic relationship and functional importance of cH and LH activity patterns were confirmed by targeted stimulation and ablation of cH neurons. Collectively, the data allow us to propose a model in which these hypothalamic nuclei regulate different phases of hunger and satiety and coordinate energy balance via antagonistic control of distinct behavioral outputs.