Presynaptic Inhibition of Gamma Lobe Neurons Is Required for Olfactory Learning in Drosophila

The loss of heterotrimeric G(o) signaling through the expression of pertussis toxin (PTX) within either the alpha/beta or gamma lobe mushroom body neurons of Drosophila results in the impaired aversive olfactory associative memory formation [1, 2]. Herein, we focus on the cellular effects of G(o) signaling in the gamma lobe mushroom body neurons during memory formation. Expression of PTX in the gamma lobes specifically inhibits G(o) activation, leading to poor olfactory learning and an increase in odor-elicited synaptic vesicle release. In the gamma lobe neurons, training decreases synaptic vesicle release elicited by the unpaired conditioned stimulus -, while leaving presynaptic activation by the paired conditioned stimulus + unchanged. PTX expression in gamma lobe neurons inhibits the generation of this differential synaptic activation by conditioned stimuli after negative reinforcement. Hyperpolarization of the gamma lobe neurons or the inhibition of presynaptic activity through the expression of dominant negative dynamin transgenes ameliorated the memory impairment caused by PTX, indicating that the disinhibition of these neurons by PTX was responsible for the poor memory formation. The role for gamma lobe inhibition, carried out by G(o) activation, indicates that an inhibitory circuit involving these neurons plays a positive role in memory acquisition. This newly uncovered requirement for inhibition of odor-elicited activity within the gamma lobes is consistent with these neurons serving as comparators during learning, perhaps as part of an odor salience modification mechanism [3-5].