ADrosophilaCircuit 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 that habituation arises from the potentiation of inhibitory inputs onto stimulus-encoding assemblies and that 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; PER) habituation. While brief sucrose contact with tarsal hairs causes naive Drosophila to extend their proboscis, persistent exposure 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 PER response to tarsal sucrose stimulation. Similar override of PER habituation can also be induced by brief thermogenetic activation of a population of tyrosine hydroxylase (TH)-positive neurons, a subset of which send projections to the subesophageal zone (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 with other findings, these observations in female flies 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.

HisCl1regulates gustatory habituation in sweet taste neurons and mediates sugar ingestion inDrosophila

“…In flies, gustatory habituation is thought to be regulated by changes in the activity of taste circuits, mainly arising from postsynaptic partners of taste neurons 1,2 . However, sweet taste neurons also adapt their firing rate during continuous optogenetic stimulation 3 or during prolonged sugar exposure (Figures S1A and S1B), suggesting there should be changes in the intrinsic properties of these neurons leading to a depression in the firing rate.…”

“… SUMMARY Similar to other animals, the fly, Drosophila melanogaster , reduces its responsiveness to tastants with repeated exposure, a phenomenon called gustatory habituation. Previous studies have focused on the circuit basis of gustatory habituation in the fly chemosensory system 1,2 . However, gustatory neurons reduce their firing rate during repeated stimulation 3 , suggesting that cell-autonomous mechanisms also contribute to habituation.…”

Sexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration

“…Thus, measuring the red:green fluorescence ratio (red:green ratio) in DA neurons within whole living fly brains enables MitoTimer to serve as an in vivo reporter of accumulating ROS during mitochondrial stress 53,54 . We imaged TH-driven MitoTimer in DAergic projections to the SOG, which are known to originate from PPM1 DA neurons 55 and local SOG DA neurons 55–57 – two DA neuron clusters that are majority dVGLUT + (Figure 1). For comparison, we also imaged DAergic projections to the ellipsoid body (EB) and fan-shaped body (FSB).…”

“…Further, we observed a regional correlation between baseline DA neuron mitochondrial oxidative stress and ATP during depolarization. DAergic projections to the SOG, which contain dVGLUT + inputs from local SOG and PPM1 DA neurons 55–57 , had the lowest mitochondrial oxidation and ATP levels. These data are consistent with mammals, as resilient VTA DA neurons (which have higher levels of VGLUT2 co-expression), have not only greater resilience to PD and mitochondrial toxin models of PD, but also 1) lower mitochondrial density, 2) lower baseline mitochondrial ROS, and 3) lower baseline oxidative phosphorylation/ATP production 104 .…”

Habituation of Sugar-Induced Proboscis Extension Reflex and Yeast-Induced Habituation Override in <em>Drosophila melanogaster</em>

“…Later studies in Drosophila and vertebrates indicate that heterosynaptic potentiation of inhibition can lead to olfactory, auditory, or gustatory habituation ( Das et al, 2011 ; Paranjpe et al, 2012 ; Ramaswami, 2014 ; Kato et al, 2015 ). However, the neural correlates of habituation override in these types of habituation are only just beginning to be investigated ( Trisal et al, 2022 ). Here, we first describe the protocol for the proboscis extension reflex (PER), which has been used previously to study gustatory habituation in Drosophila ( Duerr and Quinn, 1982 ; Le Bourg, 1983 ; Fois et al, 1991 ; Engel and Wu, 2009 ; Paranjpe et al, 2012 ), and then a protocol to induce override of PER habituation following exposure to a novel sensory stimulus ( Paranjpe et al, 2012 ; Trisal et al, 2022 ).…”