PhD Probing the structure and function of neural connectomes

Closing Date

5 Dec 2018

Address

Laboratory of Molecular Biology, Medical Research Council, Cambridge

Project Description

Connectomics offers the possibility of understanding the brain in terms of its neural components and their interactions. However, such a reductionist understanding of the brain presents many challenges. Mammalian brains contain huge numbers of neurons, and there are large gaps in our understanding of their connectivity. Moreover, extrasynaptic neuromodulatory interactions are critical for neural circuit function, but these interactions are not revealed in most connectomic reconstructions. Finally, we lack good theories to predict neural function in complex neuronal connectomes. 

We are using the nematode C. elegans, whose smaller neural connectome has been completely mapped at the cellular and synaptic levels, to discover fundamental principles of connectome structure and function. In particular, we have focused on microcircuits involved in escape and arousal, with the aim of understanding conserved computational principles implemented in larger and more complex brains. We have used theoretical approaches from network science and control theory to identify important processing hubs and predict neural function, and tested these predictions using cell ablation and in vivo neuroimaging. We are also 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, in part by identifying novel receptors and characterizing their physiology and expression patterns, 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.

Funding Notes

Please see the LMB PhD website for further details: 
View Website

References

Chew YL, Tanizawa Y, Cho Y, Zhao B, Yu AJ Ardiel EL, Rabinowitch I, Bai J, Rankin CH, Lu H, Beets I, Schafer WR (2018) 
An afferent neuropeptide system transmits mechanosensory signals triggering sensitization and arousal in C. elegans. 
Neuron in press 

Yan G, Vértes PE, Towlson EK, Chew YL, Walker DS, Schafer WR, Barabási A-L (2017) 
Network control principles predict neuron function in the C. elegans connectome 
Nature 550:519-523 

Chew YL, Walker DS, Towlson EK, Vértes PE, Yan G, Barabási A-L, Schafer WR (2017) 
Recordings of Caenorhabditis elegans locomotor behaviour following targeted ablation of single motorneurons 
Sci Data 4:170156. 

Bentley B, Branicky RS, Barnes CL, Chew YL, Yemini E, Bullmore ET, Vértes PE, Schafer WR (2016) 
The multilayer connectome of Caenorhabditis elegans 
Plos Comput Biol 12(12): e1005283 

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

Yemini E, Jucikas T, Grundy LJ, Brown AEX, Schafer WR (2013) 
A database of C. elegans behavioral phenotypes 
Nat Meth 10: 877-879. 

Brown AEX, Yemini EI, Grundy L, Jucikas T, Schafer WR (2013) 
A dictionary of behavioral motifs reveals genes affecting C. elegans locomotion 
Proc Natl Acad Sci USA 110:791-796. 

Towlson EK, Vértes PE, Ahnert SE, Schafer WR, Bullmore ET (2013) 
The rich club of the C. elegans neuronal connectom 
J Neurosci. 33: 6380-6387. 

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

Suzuki H, Thiele T, Faumont S, Ezcurra M, Lockery S, Schafer WR. (2008) 
Functional asymmetry in C. elegans salt taste neurons and its computational role in chemotaxis behaviour 
Nature 454:114-117.

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