

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 synaptic connectome has been completely mapped at the cellular level, 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.