There are often immense differences in behavior among individuals within a species and across species. This variation has been observed for centuries, but the genetic and neural mechanisms that underlie it remain undefined. We seek to define mechanistic principles on brain and behavior variation and evolution by identifying how the structure, physiology, and function of neurons and circuits differ across individuals, sex, and species to generate distinct patterns of behavior.

Our efforts are largely focused on a model system, fruit fly courtship song, that is poised to provide deep insights into the neural basis of behavior variation and evolution. Male fruit flies vibrate their wings toward females during courtship to produce a song with characteristic features that signal species identity and male quality. Fly courtship songs have evolved rapidly and extensively, which enables dozens of novel behavior patterns to be investigated in a small number of closely related species. In our previous work, we characterized the song circuit of the commonly studied fly species Drosophila melanogaster, gained precise genetic access to the neurons in this circuit, and developed novel methods to compare song neurons and the connections between them across individuals, sex, and species.

Our current work leverages these advances to identify how neuron connectivity, physiology, and function vary to generate the sex and species-specific courtship song behaviors. We accomplish this by using cutting-edge methods in genome editing, optogenetics, calcium imaging in behaving animals, expansion microscopy-based circuit reconstruction, AI-based behavior and image analyses, and electrophysiology. By precisely quantifying how neural circuit structure, physiology, and function differ across individuals and species for the first time, our research program has the potential to produce transformational advances to our understanding of brain and behavior evolution and the neural basis of behavior.

1. Lillvis JL*, Wang K, Shiozaki HM, Wu M, Stern DL, Dickson BJ* (2024) Nested neural circuits generate distinct acoustic signals during Drosophila courtship. Current Biology 34(4): 808-824.e6. https://doi.org/10.1016/j.cub.2024.01.015
2. Shiozaki HM, Wang K, Lillvis JL, Wu M, Dickson BJ, Stern DL (2024) Activity of nested neural circuits drives different courtship songs in Drosophila. Nature Neuroscience 27, 1954-1965. https://doi.org/10.1038/s41593-024-01738-9
3. Ruan X, Mueller M, Liu G, Gorlitz F, Fu T-M, Milkie DE, Lillvis JL, Kuhn A, Chong JG, Hong JL, Herr CYA, Hercule W, Nienhaus M, Killilea A, Betzig E, Upadhyayula S (2024) Image processing tools for petabyte-scale light sheet microscopy data. Nature Methods. https://doi.org/10.1038/s41592-024-02475-4
4. Sawtelle S, Narayan L, Ding Y, Kim E, Berhman EL, Lillvis JL, Kawase T, Stern DL (2024) Song Torrent: A modular, open-source 96-chamber audio and video recording apparatus with optogenetic activation and inactivation capabilities for Drosophila. bioRxiv. https://doi.org/10.1101/2024.01.09.574712
5. Lillvis JL*, Otsuna H, Ding X, Pisarev I, Kawase T, Colonell J, Rokicki K, Goina C, Gao R, Hu A, Wang K, Bogovic J, Milkie DE, Meienberg L, Boyden ES, Saalfeld S, Tillberg PW, and Dickson BJ* (2022) Rapid reconstruction of neural circuits using tissue expansion and light sheet microscopy. eLife.81248. https://doi.org/10.7554/eLife.81248
6. Tamvacakis AN, Lillvis JL, Sakurai A, Katz PS (2022) The consistency of gastropod identified neurons distinguishes intra-individual plasticity from inter-individual variability in neural circuits. Frontiers in Behavioral Neuroscience 47. https://doi.org/10.3389/fnbeh.2022.855235
7. Ding Y*, Lillvis JL*, Cande J, Berman GJ, Arthur BJ, Long X, Xu M, Dickson BJ, and Stern DL (2019) Neural Evolution of Context-Dependent Fly Song. Current Biology 29(7): 1089-1099. https://doi.org/10.1016/j.cub.2019.02.019
8. McKellar CE, Lillvis JL, Bath DE, Fitzgerald JE, Cannon JG, Simpson JH, Dickson BJ (2019) Threshold-Based Ordering of Sequential Actions During Drosophila Courtship. Current Biology 29(3): 426-434. https://doi.org/10.1016/j.cub.2018.12.019
9. Katz PS and Lillvis JL (2014) Reconciling the deep homology of neuromodulation with the evolution of behavior. Current Opinion in Neurobiology 29: 39-47. https://doi.org/10.1016/j.conb.2014.05.002
10. Lillvis JL and Katz PS (2013) Parallel evolution of serotonergic neuromodulation underlies independent evolution of rhythmic motor behavior. The Journal of Neuroscience 33(6): 2709-2717. https://doi.org/10.1523/JNEUROSCI.4196-12.2013