William Schafer

Genes, behaviour, and neuromodulatory connectomes
Group Leader page

The relationship between genes and behaviour is a fundamental problem in neuroscience. Ultimately, this requires an understanding of how specific gene products act within the context of neuronal circuitry to collect and integrate sensory information and control and pattern motor outputs. In the absence of a complete connectome, such a reductionist understanding of behaviour is difficult to achieve; however, in simpler genetically tractable organisms such as the nematode C. elegans, a molecular understanding of behaviour is an achievable goal.

We are using the worm to identify and study conserved aspects of nervous system function at the molecular and circuit levels. In particular, we have focused on microcircuits involved in sensory perception and arousal, with the aim of understanding conserved computational principles implemented in larger and more complex brains. In particular, we are interested in understanding the roles of neuromodulators, such as dopamine, serotonin, and neuropeptides, which act primarily through "wireless" signaling networks that interact in complex ways with the wired connectome. We are currently mapping these wireless connectome networks, investigating their structure and topology, and applying a broad range of approaches, including optogenetics, microfluidics, high-throughput behavioural analysis, as well as classical and molecular genetics, to determine how they control behavioural states.


References

Ezcurra, M., Walker, D.S., Beets, I., Swoboda, P. and Schafer, W.R. (2016)
Neuropeptidergic signaling and active feeding state inhibit nociception in C. elegans
J Neurosci
36: 3157-3169.

Rabinowitch, I., Laurent, P., Zhao, B., Beets, I., Schoofs, L., Bai, J., Schafer, W.R. and Treinin, M. (2016)
Neuropeptide-Driven Cross-Modal Plasticity Following Sensory Loss in C. elegans
PLoS Biol 14: e1002348.

Rabinowitch, I., Chatzigeorgiou, M., Zhao, B., Treinin, M. and Schafer, W.R. (2014)
Rewiring neural circuits by the insertion of ectopic electrical synapses in transgenic C. elegans
Nature Comm. 5: 4442.

Yemini, E., Jucikas, T., Grundy, L.J., Brown, A.E.X. and Schafer, W.R. (2013)
A database of C. elegans behavioral phenotypes
Nature Meth 10: 877-879.

Chatzigeorgiou, M., Bang, S., Hwang, S.W. and Schafer, W.R. (2013)
tmc-1 encodes a sodium-sensitive channel required for salt chemosensation in C. elegans
Nature
494: 95-99.

Chatzigeorgiou, M. and Schafer, W.R. (2011)
Lateral facilitation between primary mechanosensory neurons controls nose touch perception in C. elegans
Neuron 70: 299-309.

Ezcurra, M., Tanizawa, Y., Swoboda, P. and Schafer, W.R. (2011)
Food sensitizes C. elegans avoidance behaviors through acute dopamine signaling
EMBO Journal 30: 1110-1122.