Synapse Loss in Olfactory Local Interneurons Modifies Perception

Abstract

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.

Insulin signalling in mushroom body neurons regulates feeding behaviour inDrosophilalarvae

“…Targeted expression of a DN form of the PI3K gene under the regulation of 247-and 201y-GAL4 has been used in Drosophila adults to induce synapse loss in the mushroom body in order to evaluate the role of this structure in olfactory perception (Acebes et al, 2011). These authors report that while there is no reduction in mushroom body cell number or an effect on odorant perception in 247-or 201y-GAL4;UAS-PI3K (DN) flies, clear morphological defects were detected in their pedunculus and calyx neurites.…”

“…To direct the expression of these constructs to the larval mushroom body neurons, we used two GAL4 lines, 201y-GAL4 and 247-GAL4, identified as having the broadest expression in this structure (Pauls et al, 2010). The expression of 201y-GAL4 and 247-GAL4 is said to be mushroom body specific (Pauls et al, 2010) and as such they have been used in a number of studies addressing the function of this structure in Drosophila larval and adult behaviour (Honjo and FurukuboTokunaga, 2005;Joiner et al, 2006;Hong et al, 2008;Brembs, 2009;Honjo and Furukubo-Tokunaga, 2009;Pauls et al, 2010;Acebes et al, 2011). However, these constructs also label a small number of other neurons in the larval brain and in the case of 247-GAL4, expression in the ventral cord glia has been detected (Pauls et al, 2010).…”

“…Dou et al, 2005;Chiu et al, 2008;Oda et al, 2011) (reviewed by Chiu and Cline, 2010;Bosco et al, 2011;Kapogiannis and Mattson, 2011). In Drosophila, targeted inhibition of phosphatidylinositol 3-kinase (PI3K) was recently used to reduce synapse number to model the sensory perception decline characteristic of ageing and neurodegenerative diseases (Acebes et al, 2011). Combined, these observations prompted us to ask whether mushroom body function is required for food intake in the Drosophila foraging larva and whether these neurons are a target of insulin signalling in the context of this behaviour.…”

Learning pattern recognition and decision making in the insect brain

“…It is known that increasing odor concentrations recruit increasing numbers of glomeruli [86] and the activity of the projection neurons within the AL [87,88,89]. From the behavioral point of view, increasing the synapses of the local inhibitory neurons makes gases repulsive and to change the number of excitatory synapses makes odorants attractive [90]. This study shows how important the tight equilibrium of the excitatory and inhibitory network is in the AL.…”

Central Adaptation to Odorants Depends on PI3K Levels in Local Interneurons of the Antennal Lobe

“…All strains used here are described previously (Stocker et al, 1997;Acebes et al, 2011). Male flies were exposed during the first 5 d of adulthood to an odorant (10 Ϫ1 v/v).…”