Having a better understanding of the brain's neural connectivity will improve our understanding of the brain in normal and disease states and contribute to the development of new therapeutics. However, it is extremely difficult and time consuming to map neural connections in non-human primates and humans, where translation of the information into therapy is most efficient. Research in the Laughlin Group leverages synthetic chemistry and molecular biology principles to create new technologies for understanding the brain's neural circuity and improving human health.
The neurons that make up a circuit are linked to each other and transmit information by synapses. Shown in the black and white image above is a fluorescence micrograph of the larval zebrafish olfactory system - the neural system responsible for smell. Neurons in the nose detect odorous molecules and send a signal into the olfactory bulb, which is the first relay station for processing olfactory information in the brain. In the olfactory bulb the sensory neurons make connections, called synapses, with other neurons in order to communicate the sensory information further into the brain. The web of neural connections, or the neural circuit, is what dictates the sensory experience and any resulting behavior. Currently, these neural circuits can be very difficult to visualize.
In response to a sensory stimulus, such as a smell, sound, or sight, the neurons in a circuit burst with activity in order to process the information. At the same time, most other neurons in the brain, and in other neural circuits, are dormant. Shown in this image are neurons in the zebrafish brain responding (i.e., the red, yellow, and green colors) to chemical odorant stimuli. In the Laughlin Group, we exploit this short burst of neural activity to highlight the neural circuit responsible for processing a given sensation. In one strategy, we engineer small molecules and enzymes to permanently turn fluorescent in response to a burst of neural activity. By applying thes tools to the brain and exposing the animal to an interesting smll, sound or sight, we make only those neurons resposible for processing the sensation fluorescent, allowing us to image the neural circuit at high resolution.
Small Molecule Control of Behavior
The brain detects most sensory stimuli with a complex array of sensory neurons. However, some sensations can be reduced to a single, perfectly-defined molecule structure. In our research, we search for molecular structures that cause instinctive behaviors in small animal models like larval zebrafish. These behaviorally active molecules give us exquisite control over the neural circuits for behaviors like fear and anxiety, allowing us to dissect their neural circuits using the above chemical strategies and apply our findings to improving human health.
