A DROSOPHILA CIRCUIT FOR HABITUATION OVERRIDE

Habituated animals retain a latent capacity for robust engagement with familiar stimuli. In most instances, the ability to override habituation is best explained by postulating: (a) that habituation arises from the potentiation of inhibitory inputs onto stimulus-encoding assemblies; and (b) fast habituation override occurs through disinhibition. Previous work has shown that inhibitory plasticity contributes to specific forms of olfactory and gustatory habituation in Drosophila. Here we analyze how exposure to a novel stimulus causes override of gustatory (proboscis-extension reflex or "PER") habituation. While brief sucrose contact with tarsal hairs causes naive Drosophila to extend their proboscis, persistent tarsal exposure to sucrose reduces PER to subsequent sucrose stimuli. We show that in so habituated animals, either brief exposure of the proboscis to yeast or direct thermogenetic activation of sensory neurons restores the PER response to tarsal sucrose stimulation. Similar override of PER habituation can also be induced by brief thermogenetic activation of a population of TH (Tyrosine-Hydroxylase) positive neurons, a subset of which send projections to the SEZ. Significantly, sensory-neuron induced habituation override requires transmitter release from these TH-positive cells. Treatments that cause override specifically influence the habituated state, with no effect on the naive sucrose response across a range of concentrations. Taken together, these and other findings are consistent with a model in which novel taste stimuli trigger activity in dopaminergic neurons which, directly or indirectly, inhibit GABAergic cells that drive PER habituation. The implications of these findings for general mechanisms of attentional and sensory override of habituation are discussed. SIGNIFICANCE STATEMENTBehavioral habituation can be overcome when a new context requires an enhanced response to a familiar stimulus. However, the underlying mechanisms remain incompletely understood. Previous studies have provided evidence that habituation of the sucrose-induced proboscis extension reflex (PER) in Drosophila occurs through potentiation of inhibition onto the PER pathway. This work defines controlled protocols for override of PER habituation and uses them to outline the underlying circuit mechanisms. The results presented support a model in which novel taste stimuli cause dishabituation by activating a subset of tyrosine-hydroxylase-expressing neurons that inhibit GABAergic neurons whose potentiation underlies PER habituation. At a general level, these findings further highlight a central role for inhibition and disinhibition in the control of behavioral flexibility.