| Summary: | <p>Abstract</p> <p>Background</p> <p>In vertebrates and invertebrates, sensory neurons adapt to variable ambient conditions, such as the duration or repetition of a stimulus, a physiological mechanism considered as a simple form of non-associative learning and neuronal plasticity. Although various signaling pathways, as cAMP, cGMP, and the inositol 1,4,5-triphosphate receptor (InsP<sub>3</sub>R) play a role in adaptation, their precise mechanisms of action at the cellular level remain incompletely understood. Recently, in <it>Drosophila</it>, we reported that odor-induced Ca<sup>2+</sup>-response in axon terminals of olfactory receptor neurons (ORNs) is related to odor duration. In particular, a relatively long odor stimulus (such as 5 s) triggers the induction of a second component involving intracellular Ca<sup>2+</sup>-stores.</p> <p>Results</p> <p>We used a recently developed <it>in-vivo </it>bioluminescence imaging approach to quantify the odor-induced Ca<sup>2+</sup>-activity in the axon terminals of ORNs. Using either a genetic approach to target specific RNAs, or a pharmacological approach, we show that the second component, relying on the intracellular Ca<sup>2+</sup>-stores, is responsible for the adaptation to repetitive stimuli. In the antennal lobes (a region analogous to the vertebrate olfactory bulb) ORNs make synaptic contacts with second-order neurons, the projection neurons (PNs). These synapses are modulated by GABA, through either GABAergic local interneurons (LNs) and/or some GABAergic PNs. Application of GABAergic receptor antagonists, both GABA<sub>A </sub>or GABA<sub>B</sub>, abolishes the adaptation, while RNAi targeting the GABAB<sub>R </sub>(a metabotropic receptor) within the ORNs, blocks the Ca<sup>2+</sup>-store dependent component, and consequently disrupts the adaptation. These results indicate that GABA exerts a feedback control. Finally, at the behavioral level, using an olfactory test, genetically impairing the GABA<sub>B</sub>R or its signaling pathway specifically in the ORNs disrupts olfactory adapted behavior.</p> <p>Conclusion</p> <p>Taken together, our results indicate that a relatively long lasting form of adaptation occurs within the axon terminals of the ORNs in the antennal lobes, which depends on intracellular Ca<sup>2+</sup>-stores, attributable to a positive feedback through the GABAergic synapses.</p>
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