Synapse Loss in Olfactory Local Interneurons Modifies Perception

Synapse loss correlates with cognitive decline in aging and most neurological pathologies. Sensory perception changes often represent subtle dysfunctions that precede the onset of a neurodegenerative disease. However, a cause-effect relationship between synapse loss and sensory perception deficits is difficult to prove and quantify due to functional and structural adaptation of neural systems. Here we modified a PI3K/AKT/GSK3 signaling pathway to reduce the number of synapses-without affecting the number of cells-in five subsets of local interneurons of the Drosophila olfactory glomeruli and measured the behavioral effects on olfactory perception. The neuron subsets were chosen under the criteria of GABA or ChAT expression. The reduction of one subset of synapses, mostly inhibitory, converted the responses to all odorants and concentrations tested as repulsive, while the reduction of another subset, mostly excitatory, led to a shift toward attraction. However, the simultaneous reduction of both synapse subsets restored normal perception. One group of local interneurons proved unaffected by the induced synapse loss in the perception of some odorants, indicating a functional specialization of these cells. Using genetic tools for space and temporal control of synapse number decrease, we show that the perception effects are specific to the local interneurons, rather than the mushroom bodies, and are not based on major structural changes elicited during development. These findings demonstrate that synapse loss cause sensory perception changes and suggest that normal perception is based on a balance between excitation and inhibition.