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

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 Drosophila melanogaster, 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.

Dopamine Modulates Serotonin Innervation in the Drosophila Brain.

Parkinson's disease (PD) results from a progressive degeneration of the dopaminergic nigrostriatal system leading to a decline in movement control, with resting tremor, rigidity and postural instability. Several aspects of PD can be modeled in the fruit fly, Drosophila melanogaster, including α-synuclein-induced degeneration of dopaminergic neurons, or dopamine (DA) loss by genetic elimination of neural DA synthesis. Defective behaviors in this latter model can be ameliorated by feeding the DA precursor L-DOPA, analogous to the treatment paradigm for PD. Secondary complication from L-DOPA treatment in PD patients are associated with ectopic synthesis of DA in serotonin (5-HT)-releasing neurons, leading to DA/5-HT imbalance. Here we examined the neuro-anatomical adaptations resulting from imbalanced DA/5-HT signaling in Drosophila mutants lacking neural DA. We find that, similar to rodent models of PD, lack of DA leads to increased 5-HT levels and arborizations in specific brain regions. Conversely, increased DA levels by L-DOPA feeding leads to reduced connectivity of 5-HT neurons to their target neurons in the mushroom body (MB). The observed alterations of 5-HT neuron plasticity indicate that loss of DA signaling is not solely responsible for the behavioral disorders observed in Drosophila models of PD, but rather a combination of the latter with alterations of 5-HT circuitry.