The overall goal of our research is to discover the circuit implementation of learning and action selection.  Since these functions likely emerge from parallel and distributed computations across many interconnected brain areas, over the past five years we have established an approach that involves combining comprehensive brain-wide analysis of structure and function in the tractable Drosophila larva. Recently we have generated a comprehensive synaptic-resolution wiring diagram of the entire brain and a comprehensive genetic toolkit for the selective manipulation of each uniquely identified neuron type.  Possible PhD projects will involve 1) identifying the patterns of activity in individual neurons in the brain that correlate with the formation of specific memories and/or the selection of specific actions, using light-sheet and two-photon imaging of neural activity or patch-clamp recordings; 2) testing whether the candidate neurons are required and sufficient for learning and action selection by manipulating them using optogenetics or thermogenetics in freely behaving animals; 3) identifying genes required for learning and memory in specific neurons using RNAseq and testing whether they are required using targeted knockdown.

References

Winding, M., Pedigo, B.D., Barnes, C.L., Patsolic, H.G., Park, Y., Kazimiers, T., Fushiki, A., Andrade, I.V., Khandelwal, A., Valdes-Aleman, J., Li, F., Randel, N., Barsotti, E., Correia, A., Fetter, R.D., Hartenstein, V., Priebe, C.E., Vogelstein, J.T., Cardona, A., Zlatic, M. (2023)
The connectome of an insect brain
Science 379(6636): eadd9330

Eschbach, C., Fushiki, A., Winding, M., Afonso, B., Andrade, I.V., Cocanougher, B.T., Eichler, K., Gepner, R., Si, G., Valdes-Aleman, J., Fetter, R.D., Gershow, M., Jefferis, G.S., Samuel, A.D., Truman, J.W., Cardona, A., Zlatic, M. (2021)
Circuits for integrating learned and innate valences in the insect brain
Elife 10: e62567

Eschbach, C., Fushiki, A., Winding, M., Schneider-Mizell, C.M., Shao, M., Arruda, R., Eichler, K., Valdes-Aleman, J., Ohyama, T., Thum, A.S., Gerber, B., Fetter, R.D., Truman, J.W., Litwin-Kumar, A., Cardona, A., Zlatic, M. (2020)
Recurrent architecture for adaptive regulation of learning in the insect brain
Nat Neurosci 23(4): 544-555

Eschbach, C., Zlatic, M. (2020)
Useful road maps: studying Drosophila larva's central nervous system with the help of connectomics
Curr Opin Neurobiol 65: 129-137

Valdes-Aleman J., Fetter R. D., Sales E. C., Heckman E. L., Doe C. Q., Landgraf M., Cardona A. and Zlatic M. (2021)
Synaptic specificity is collectively determined by partner identity, location and activity.
Neuron 109(1):105-122.e7. doi: 10.1016/j.neuron.2020.10.004.

Eichler, K., Li, F., Litwin-Kumar, A., Park, Y., Andrade, I., Schneider-Mizell, C.M., Saumweber, T., Huser, A., Eschbach, C., Gerber, B., Fetter, R.D., Truman, J.W., Priebe, C.E., Abbott, L.F., Thum, A.S., Zlatic, M., Cardona, A. (2017)
The complete connectome of a learning and memory centre in an insect brain
Nature 548(7666): 175-182

Jovanic, T., Schneider-Mizell, C.M., Shao, M., Masson, J., Denisov, G., Fetter, R.D., Mensh, B.D., Truman, J.W., Cardona, A., Zlatic, M. (2016)
Competitive Disinhibition Mediates Behavioral Choice and Sequences in Drosophila
Cell 167(3): 858-870

Ohyama, T., Schneider-Mizell, C.M., Fetter, R.D., Aleman, J.V., Franconville, R., Rivera-Alba, M., Mensh, B.D., Branson, K.M., Simpson, J.H., Truman, J.W., Cardona, A., Zlatic, M. (2015)
A multilevel multimodal circuit enhances action selection in Drosophila
Nature 520(7549): 633-9