Periodic Reporting for period 4 - MultiSense (Multisensory signal processing: From brain-wide neuronal circuits to behavior)
Berichtszeitraum: 2021-09-01 bis 2023-08-31
Our brain needs to constantly fuse sensory information detected by our multiple senses to produce a seamless coherent representation of the world. Rather than being the exception, this binding process is ubiquitous to sensory-motor integration and is implicated in most cognitive functions. Its impairment is a cause of various pathologies, such as schizophrenia or autism. Multisensory processing operates on all brain levels from primary cortices over subcortical structures up to higher associative centers, while the smallest operational units are single multisensory neurons. In an interdisciplinary effort, we combine optical developments, genetics, and neuro-computation to obtain new insights into the activity of brain-wide neural circuits that process multisensory information. To reduce the complexity, we study the small transparent brain of zebrafish larvae as a model system. Our research particularly examines gaze stabilization, a multisensory task inherent to all vertebrates. This reflex integrates vestibular and visual inputs to control eye movements, compensating for self-motion and ensuring visual clarity. In this project, we have developed a series of innovative experimental platforms that allow for the integration of vestibular stimulation with high-resolution, brain-wide neural activity recordings. Our pioneering efforts have mapped the vertebrate brain's global response to vestibular stimuli related to roll and pitch movements. By combining vestibular and visual stimuli in various multisensory scenarios—coherent, asynchronous, or conflicting—we have identified multisensory neurons and assessed their functional significance across the brain. Through in silico studies employing minimal spiking neural network models, we have examined the roles of multisensory neurons in a variety of tasks. Our findings suggest that while multimodal units may not be necessary for achieving accuracy or managing the speed-accuracy trade-off in traditional multisensory tasks, they are indispensable for tasks requiring the detection of comodulation across sensory channels. Additionally, our work has led to the deduction of brain-wide functional connectivity, utilizing generative network modeling based on recorded brain activity. With the introduction of an innovative all-optical platform for optogenetic circuit interrogation, our ongoing work is aimed at further delineating these multisensory networks and confirming computational predictions emanating from our models.
First, we developed an ultra-stable rotating one-photon light-sheet microscope that overcame the standing challenge to make functional whole-brain imaging compatible with physiological vestibular stimulation. It is based on a novel miniaturized light-sheet unit that is mounted on a rotating stage—the unit can additionally be mounted as light-sheet module on standard microscopes. Co-rotating the tethered fish and the microscope stimulates the vestibular system while maintaining stable imaging conditions. With the system, we mapped, for the first time, the brain-wide response of larval zebrafish to vestibular rolling stimuli and identified three major functional clusters that exhibit well-defined phasic and tonic response patterns (Migault et al. Current Biology 2018).
Second, we gained high control over the visual environment of the fish by developing a two-photon version of the system based on an infrared light-sheet for which the fish is blind so that the laser light-sheet does not excite the photoreceptors in the fish eye. The challenge was to fiber deliver the femtosecond pulsed laser required for two-photon microscopy onto our rotating light-sheet platform. We achieved broadband and dispersion free laser delivery with a hollow-core negative curvature fiber. This fiber should find additional application in head mounted miniscopes for the excitation of a large spectrum of optogenetic and fluorescent proteins via a single fiber or to share the high cost laser source required for two-photon microscopy between different setups. With our rotatable two-photon system, we succeeded to mapped, for the first time, the pure brain-wide vestibular response of larval zebrafish to dynamic tilt stimuli (Trentesaux et al. manuscript in preparation).
Second, we gained high control over the visual environment of the fish by developing a two-photon version of the system based on an infrared light-sheet for which the fish is blind so that the laser light-sheet does not excite the photoreceptors in the fish eye. The challenge was to fiber deliver the femtosecond pulsed laser required for two-photon microscopy onto our rotating light-sheet platform. We achieved broadband and dispersion free laser delivery with a hollow-core negative curvature fiber. This fiber should find additional application in head mounted miniscopes for the excitation of a large spectrum of optogenetic and fluorescent proteins via a single fiber or to share the high cost laser source required for two-photon microscopy between different setups. With our rotatable two-photon system, we succeeded to mapped, for the first time, the pure brain-wide vestibular response of larval zebrafish to dynamic tilt stimuli (Trentesaux et al. manuscript in preparation).
With our rotating one- and two-photon rotating light-sheet microscopy platform, we have developed an unconventional methodology. With the system brain-wide neuronal activity recordings during dynamic vestibular stimulation are now possible. We are the only lab in the world that has such a system at hand and we use this system now to characterize vestibular processing in the brain and to study how this pathway is integrated with visual information when animals interact in a virtual vestibular-visual environment comparable to a flight simulator for pilot training.