Nitric oxide signaling modulates cholinergic synaptic input to projection neurons in Drosophila antennal lobes

Biochemical investigations have demonstrated that nitric oxide synthase (NOS) is distributed widely in the olfactory system. However, little is known about the action of NO at the synaptic level on identified neurons in local circuits that process chemosensory signals. Here, using whole-cell recordings, the effect of NO on cholinergic synaptic input to olfactory projection neurons (PNs) is determined in the Drosophila antennal lobes (ALs), which has become an excellent model for studying early olfactory-processing mechanisms. We found that the NO donor SNP/SNAP or the NO precursor L-arginine significantly decreased the frequency of cholinergic spontaneous excitatory postsynaptic currents (sEPSCs) in PNs. Conversely, soluble guanylyl cyclase (sGC) inhibitor oxadiazolo-quinoxaline-one (ODQ) significantly increased the frequency of cholinergic sEPSCs in PNs. The subsequent application of 8-bromo-cGMP significantly attenuated the effects of ODQ, indicating the possible involvement of NO-cGMP signaling. To determine the role of NO in quantal release of acetylcholine (Ach) to PNs, cholinergic miniature excitatory postsynaptic currents (mEPSCs) were recorded. SNP significantly decreased the frequency of mEPSCs, but exhibited no effect on the amplitude or the decay time constant of mEPSCs in PNs. The effect of SNP on the frequency of mEPSCs could be eliminated by ODQ as well. Thus, these results suggest that elevated NO concentration decreased cholinergic synaptic input to PNs in a sGC-dependent manner. In this way, NO signaling is suited to fulfill a regulatory role to effectively fine-tune network activity in Drosophila ALs.