The overarching theme of Baier’s scientific contributions to neuroscience has been the elucidation of molecular, cellular, synaptic and circuit mechanisms of nervous system function and animal behavior. The following questions are of particular interest:
What are the specific functions of neuronal cell types in perception and behavior?
How is circuit organization and composition related to behavioral function?
How are neural circuits modulated and integrated into wider networks to orchestrate complex, flexible behavior?
How do neurons become different during development? How are their processes guided to their targets, and how do they form specific synaptic connections?
Herwig Baier's work led to a number of scientific discoveries:
Establishing zebrafish for neuroscience: Since the early 1990s, Baier pioneered the use of zebrafish, as an experimental model for neuroscience and behavioral genetics, taking advantage of the optical transparency of these animals at larval stages and their genetic modifiability. This work led to the first large-scale behavioral screens in search of genes that wire the visual system for behavior. '
Molecular and cellular mechanisms underlying the formation of retinotopic and visual feature maps: Baier contributed to the identification of gradient-based axon guidance mechanisms during development of the visual system. His group also discovered the role of Slit-Robo signaling in the precise targeting of layers in the optic tectum by ingrowing retinal axons. '
Cell fate decisions in the developing visual system: Baier discovered the role of interkinetic nuclear migration in apportioning cell fates in the retina. '
Remote optical control of behavior: Baier's group was the first to use optogenetic techniques for circuit analysis in zebrafish. By targeting the expression of fluorescent indicators and optogenetic effectors, such as Channelrhodopsin, Halorhodopsin or the light-activated glutamate receptor, to specific brain areas and shining light at single neurons, he and his collaborators showed that an animal's behavior can be reversibly and specifically altered on millisecond timescales. '
Two-photon optogenetics with 3D resolution in the intact brain of a behaving animal: In 2017, Baier’s team introduced an optical technique that enables precise remote control of neural activity, called two-photon holographic optogenetics. By inserting a spatial light modulator into the optical path of a two-photon microscope, the technique allows to photostimulate an arbitrary population of single neurons in the zebrafish brain while observing the resulting behavior. This method is instrumental for the functional annotation of neural circuits.
In 2001, Herwig Baier co-founded, with Bill Harris and Paul Goldsmith, Daniolabs Ltd, a biotech company with a focus on zebrafish drug screening for the discovery new treatments of ophthalmic, neurological and gastrointestinal diseases. Baier serves as a scientific consultant to biotech companies.