Science
Our major scientific focus is on the olfactory system of mice. We choose this system because it presents a tractable “playground” for so many of the questions of modern neuroscience:
- How are individuals recognized? In olfaction, we can literally enumerate the cues, and we can return to the same cells or circuits again and again.
- How do individuals differ? We have discovered that experience shapes the nervous system in surprising ways.
- How do circuits compute? Odors present a “ligogenetic” toolbox of unparalleled specificity for manipulating inputs to downstream circuits. Cortico-striatal interactions lie within a few synapses of the periphery, and the ability to exhaustively characterize all inputs means that we can recognize how different neurons develop their response properties.
- How are jobs apportioned among molecules, membranes, and synapses? With a clear and quantitative understanding it becomes possible to understand key aspects of behavior down to molecular detail.
Technology
We have developed several technologies with unusual impact:
- We are among the independent inventors of light sheet microscopy, and the first to use it for large-scale calcium imaging (Holekamp et al, 2008). Trainees in the lab routinely record from tens of thousands of neurons in each experiment.
- To handle our large data sets, we helped develop a new programming language, Julia. Julia is already being used by hundreds of thousands of people, and is growing at a phenomenal rate. We are among the top developers and designers of the core language worldwide, and the authors of more than a hundred packages.
- We developed Component Activity Matching, a method for identifying key molecules among complex mixtures containing thousands of different chemicals.
- Soon-to-be published contributions include “PhOTseq,” a new method for optically tagging individual neurons in intact circuits for later study by sequencing, and a host of new mathematical and software tools for optimization and machine learning.