Animals must locate food to survive and appropriate sexual partners with whom to reproduce. At the same time they must avoid predators and pathogens that threaten their survival, or the survival of their offspring. Recognising salient environmental cues is therefore critical to fitness-related behaviours. In many cases, certain stimuli evoke stereotypical behavioural responses. These innate behaviours, in contrast to learned behaviours, are thought to be hardwired in the neural circuitry of an animal. How are these innate behavioural responses instantiated in the circuitry of the brain?

We used the olfactory sensory circuit of a microbial odorant, geosmin, as a model to understand how an innately aversive olfactory signal is processed in the brain in order to produce an appropriate behavioural response. We used connectomics, functional imaging, and behavioural assays to determine the anatomy and function of this geosmin processing circuitry. Using behavioural assays, we show that the aversive response to geosmin is due to chemotaxis, and provide evidence of a post-mating switch in behavioural response to geosmin. We then show that geosmin is detected via a functionally segregated pathway in the sensory periphery until it reaches the central brain, where the signal diverges significantly, and use connectomics to show that this divergent connectivity is largely stereotyped. We then imaged the activity of one previously described third-order neuron downstream of the geosmin pathway to show that it integrates olfactory signals of similar ethological significance at its dendrites.

We used connectomics to follow this circuit deeper into the brain, and discovered a previously unknown descending neuron that senses geosmin, and is required for the innate aversion to geosmin exhibited during egg-laying. Connectomics analysis showed that this cell converges with other descending neurons in the ventral nerve cord of the fly that are known to induce escape behaviours. We further find evidence of a learned innate interaction via memory input to this descending neuron, implicating this circuit in aversive memory recall.

These findings extend our understanding of how aversive signals are processed by the brain by providing a functional and connectomic characterisation of an olfactory circuit all the way from the brain to the nerve cord.