Biased randomness: a fundamental connectivity mechanism for associative brain centers.

PROJECT SUMMARY Uncovering fundamental mechanisms of neuronal connectivity that enable associative brain centers to learn efficiently is an important goal of neuroscience. In the mushroom body — the associative brain center in Drosophila melanogaster — the constituent Kenyon cells receive input from olfactory projection neurons. Each projection neuron connects to one of the 51 glomeruli forming the antennal lobe, the primary olfactory processing center in the Drosophila brain. Our previous work has shown that these connections are random in that there are no sets of glomeruli converging preferentially onto a given Kenyon cell. However, the glomeruli are not represented with equal frequency among Kenyon cell inputs. Certain glomeruli are significantly overrepresented or underrepresented, even though a uniform distribution would be optimal for learning performance. We are proposing to test the hypothesis that this non-uniform distribution — which we call 'biased randomness' — serves an important biological function, namely to predispose the learning ability of the mushroom body towards certain ethologically pertinent stimuli. To test this hypothesis, we will first compare the representation of individual glomeruli in different Drosophila populations that have evolved in different environments in order to investigate whether there are correlations between biases and known differences in chemosensory ecology (Aim 1). Second, molecular regulators of glomerular representation will be identified in Drosophila melanogaster to manipulate the representation of individual glomeruli and test for effects on olfactory representation in the mushroom body and learning (Aim 2). The research in this proposal has the potential to reveal a fundamental mechanism by which neuronal connectivity is fine-tuned to predispose learning towards particularly pertinent stimuli and that underlies the evolution of neuronal circuit architecture in different chemosensory environments.