Genes - Circuits - Behavior
All sensory perception and every coordinated movement, as well as feelings, memories and motivation, arise from the bustling activity of many millions of interconnected cells in the CNS. The ultimate function of this elaborate network is to generate behavior. The goal of our research is to understand how neuronal circuits convert sensory inputs into behavioral responses.
We use zebrafish as our experimental model. Zebrafish larvae are tiny vertebrates, just a few millimeters in length from head to tail, but they are effective hunters of even smaller organisms. When a single-celled paramaecium swims into view, the animal turns towards it, pursues it and captures it by sucking it into his mouth. We recently discovered that a moving dot that is displayed on a miniature computer screen is able to elicit a sequence of movements that resembles prey capture. The animal swims toward the wiggling dot on the screen in front of it, in an apparent attempt to catch this “virtual prey”. However, when the dot on the screen is not behaving like potential food but is rather expanding in size, simulating an approaching object, then the fish reacts by making an escape turn to avoid the expected collision. A third behavior, the optokinetic response, is evoked by a set of space-filling black-and-white stripes that move around the fish. In this situation, the animal’s eyes make jerky movements from side to side in pursuit of the drifting grating. Thus, specific visual stimulus configurations release particular behaviors. How does the brain distinguish between these stimuli and activate the appropriate motor programs?
To tackle these questions experimentally, we employ a diverse array of methods. All our approaches take advantage of the feature that zebrafish larvae are optically transparent. We are generating transgenic animals that express genetically encoded, fluorescent reporters that indicate changes in neuronal activity. With the help of two-photon microscopy, we can then watch neurons in the fish brain process visual stimuli and generate motor commands. Optogenetic perturbation experiments, with Channelrhodopsin, Halorhodopsin and other actuators, then tell us if a part of the nervous system, e. g., a neuronal cell type or a region of the brain, is necessary for a particular behavior. Pulses of focused laser light, applied through the skin of the intact animal, can turn on or off groups of neurons. This approach allows for the remote optical control of neuronal activity with spectacular resolution in space and time. We are currently working on novel optical methods that should allow us to elicit a specific behavior in a fish that is looking at a blank screen by “re-playing” the brain activity that is normally associated with sensory perception.
Unsurprisingly, even fish larvae make choices in life. A few examples: When they are hungry, they are more eager to hunt. When they are stressed, they may become anxious or unresponsive. When they remember a place where they have recently found food, they are more likely to return there. Our group is investigating these elementary manifestations of motivation, emotion and cognition in the fish brain.
The wiring pattern of neurons in every area of the brain is not random, but highly specific. While the number of neurons may be staggering, they appear to fall into a finite number of cell types, which are in turn wired up with other types of neurons in a regular manner. Complementing our work on the remote optical control of behavior, we are also devising methods to identify the molecular mechanisms underlying neuronal diversity and synaptic specificity in the CNS. In summary, through our research, we want to find out how genes assemble neuronal circuits and how these circuits in turn control behavior.