Synaptic connectomes of model nervous systems: their collection and utility

Abstract: The brain is a network of neurons and its biological output is behaviour. We have entered an exciting age in neurobiology, with the growing reality that the comprehensive compilation of synaptic circuits densely reconstructed in model brains is now both technologically feasible and a scientifically enabling possibility in neurobiology, much as 30 years ago genomics was in molecular biology and genetics. Implemented by huge advances in EM technology, and computer-aided reconstruction of neuron morphologies, the last decade has witnessed enormous progress in detailed knowledge of the actual synaptic circuits formed by real neurons. Examples come from various brain regions of the fly Drosophila and the tiny brain of the ascidian tadpole larva Ciona intestinalis. Synaptic pathways are either major, with 100 or more contacts, or minor, with fewer than 10; most neurites are both pre- and postsynaptic; and synaptic sites may have multiple postsynaptic dendrites. Work on Drosophila has spearheaded these advances because cell numbers are manageable, and neuron classes discrete and identifiable, and confirmed by genetic reporters. The value of a complete connectome in Drosophila is that, by targeting to specific neurons transgenes that either silence or activate morphologically identified circuits, and then identifying the resulting behavioural outcome, we can determine the causal mechanism for behaviour from its loss or gain. More important, the connectome reveals hitherto unsuspected pathways, leading us to seek novel behaviours for these. Circuit information will eventually be required to understand how differences between brains underlie differences in behaviour, or to identify common synaptic circuits in different species.