Stochastic and Arbitrarily Generated Input Patterns to the Mushroom Bodies Can Serve as Conditioned Stimuli in .

Single neurons in the brains of insects often have individual genetic identities and can be unambiguously identified between animals. The overall neuronal connectivity is also genetically determined and hard-wired to a large degree. Experience-dependent structural and functional plasticity is believed to be superimposed onto this more-or-less fixed connectome. However, in , it has been shown that the connectivity between the olfactory projection neurons (OPNs) and Kenyon cells, the intrinsic neurons of the mushroom body, is highly stochastic and idiosyncratic between individuals. Ensembles of distinctly and sparsely activated Kenyon cells represent information about the identity of the olfactory input, and behavioral relevance can be assigned to this representation in the course of associative olfactory learning. Previously, we showed that in the absence of any direct sensory input, artificially and stochastically activated groups of Kenyon cells could be trained to encode aversive cues when their activation coincided with aversive stimuli. Here, we have tested the hypothesis that the mushroom body can learn any stochastic neuronal input pattern as behaviorally relevant, independent of its exact origin. We show that fruit flies can learn thermogenetically generated, stochastic activity patterns of OPNs as conditioned stimuli, irrespective of glomerular identity, the innate valence that the projection neurons carry, or inter-hemispheric symmetry.