A Drosophila Circuit for Habituation Override

Abstract

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 naīve 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 naīve 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.

Functional and pharmacological analyses of visual habituation learning in larval zebrafish

“…A critical role for GABA in habituation is consistent with data from Drosophila , where both olfactory and gustatory habituation have been linked to GABAergic interneurons ( Das et al, 2011; Paranjpe et al, 2012; Trisal et al, 2022 ). Therefore, this circuit motif of increasing inhibition to drive habituation may be a conserved feature of habituation, which would allow for a straightforward mechanism for habituation override during dis-habituation via dis-inhibition ( Cooke and Ramaswami, 2020; Trisal et al, 2022 ).…”

“…Physiological and genetic work in Aplysia , and C. elegans were consistent with a model in which homosynaptic depression of excitatory synapses drives habituation ( Bailey and Chen, 1983 ; Rose et al, 2003 ) ( although see ( Glanzman, 2009 )). In contrast, work in the Drosophila olfactory and gustatory systems indicate that the potentiation of inhibitory neurons drives habituation rather than depression of excitatory connections ( Das et al, 2011 ; Paranjpe et al, 2012 ; Trisal et al, 2022 ), and habituation to specific orientations of visual cues in mice is associated with the potentiation of neuronal activity and synapses in the visual cortex ( Cooke et al, 2015 ), which requires GABAergic interneurons ( Kaplan et al, 2016 ; Hayden et al, 2021 ). These studies are more consistent with a model in which the potentiation of inhibition, rather than depression of excitation, drives habituation ( Cooke and Ramaswami, 2020 ).…”