Univ.-Prof. Dr. Manuel Zimmer
Our research group is located at the University of Vienna. The Zimmer group aims to uncover fundamental principles of brain function by studying model organisms with small brains, such as the nematode Caenorhabditis elegans, with a nervous system of only 302 neurons, and the tiny transparent fish Danionella cerebrum, one of the smallest known vertebrates with a brain of approximately 650,000 neurons.
Research areas:
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Motor control. Using large-scale neuronal imaging, we study how intrinsic neuronal network dynamics in the brain operate over multiple time scales to generate organized action sequences and motor patterns. We also investigate how sensory information is processed through these dynamics to enable sensory-driven behaviors.
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Social behaviors. The fish D. cerebrum exhibits elaborate reproductive social behaviors including male-male and male-female interactions. Using advanced behavioral recording techniques, we investigate these behaviors and how animals communicate via acoustic and pheromonal cues.
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Sleep and wakefulness. How do animals switch-between and maintain drastically different brain states? We address these problems via single-cell resolution brain-wide neuronal activity imaging in C. elegans and D. cerebrum.
Focal points of interest
Large-scale recordings of neuronal activity in various model species have shown that brain activity is typically characterized by rich and distributed neuronal dynamics. However, individual neurons, circuits, or entire brain regions do not act in isolation, but rather are tightly coordinated with each other to generate organized activity patterns such as network oscillations and other attractor dynamics. Such coordinated network dynamics are thought to require a balance between excitatory and inhibitory neuronal circuits, but the exact mechanisms remain elusive.
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We will use the tractable model system C. elegans to identify and characterize the excitatory and inhibitory cell types required for patterned network activity. We will focus on the involved GABA cells and other functionally analogous inhibitory cell types. Our goal is to achieve a realistic network simulation of the nematode brain.
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The fish Danionella cerebrum provides a unique opportunity to monitor brain-wide activity at single cell resolution throughout development, from larval stages to adulthood. We will study the ontogeny of intrinsic brain dynamics with a focus on the functional specification of diverse GABAergic cell types.
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We will study the ontogeny of network dynamics in human cerebral organoids (in collaboration with Jürgen Knoblich).
Technical proficiency and instrumentation
We are applying and developing advanced microscopy approaches for rapid volumetric recording of brain activity, such as an oblique plane light sheet microscope and customized spinning disk confocal and 2-photon microscopes. We are working on optimized solutions for simultaneous recording of unconstrained behavior and whole brain single-cell resolution neuronal activity. Further, we develop technologies enabling patterned closed-loop photo-stimulation for optogenetics.
We moreover provide expertise in state-of-the-art machine vision tools to extract high-content neural and behavioral time series from large-scale neural and behavioral video recordings. We also develop and apply advanced computational methods to analyze complex behavioral and neural data sets.
Aspirations for the next 5 years
Our vision for the next 5 years is to use the tractable C. elegans model to gain a mechanistic understanding of how coordinated network activity arises in the brain and to uncover the functions of brain-wide coordinated activity patterns. In our fish research, we aim to establish new social behavior paradigms for this model and to investigate the neuronal mechanisms underlying complex social interactions such as courtship and male-male competition. Using both nematodes and fish, we aim to elucidate the neuronal mechanisms that control longer-lasting behavioral states such as arousal, wakefulness, and sleep.
References
- Uzel K, Kato S, Zimmer M. (2022). A set of hub neurons and non-local connectivity features support global brain dynamics in C. elegans. Current Biology. 32(16): 3443-3459 e3448.doi: https://doi.org/10.1016/j.cub.2022.06.039. PMID: 35809568.
- Kaplan HS, Salazar Thula O, Khoss N, Zimmer M (2020). Nested neuronal dynamics orchestrate a behavioral hierarchy across timescales. Neuron. 105(3), 562–576.e9. http://doi.org/10.1016/j.neuron.2019.10.037
- Nichols ALA, Eichler T, Latham R, Zimmer M (2017). A global brain state underlies C. elegans sleep behavior. Science 356, eaam6851. https://doi.org/10.1126/science.aam6851
