Early in his career, Karl has worked on elucidating the neural substrates of sleep either studying everything from whales to humans, rodent and later zebrafish. Initially to further establish the zebrafish as an appropriate model system for studying sleep was as significant part of the early work. The core methods emplyoed include automated behavioral analysis, basic genetics, histology and in vivo/in vitro electrophysiology.
The core questions revolve around elucidating the neural substrates of sleep in this teleost fish, comparing them to what is known in mammals; revealing the state-dependent genetic expression in zebrafish and to clarify the role of sleep in various aspects of neural plasticity. Some aspects of the work has turned out to have practical applications. Currently, zebrafish models of human sleep disorders are generated, behavioral parameters that best differentiate between wildtype and mutated (typically using CRISPR) fish are generated. Then we employ our high-throughput behavioral screening technology to identify compounds that could modulate the human condition.