Driver lines for studying associative learning in Drosophila

Shuai, Yichun; Sammons, Megan; Sterne, Gabriella R; Hibbard, Karen; Yang, He; Yang, Ching-Po; Managan, Claire; Siwanowicz, Igor; Lee, Tzumin; Rubin, Gerald M.; Turner, Glenn C; Aso, Yoshinori

doi:10.1101/2023.09.15.557808

Cited by 10 publications

(4 citation statements)

References 146 publications

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“…Alternatively, different subsets of Gr64f-Gal4 -expressing neurons may promote opposing behaviors, as suggested by a recent study, 46 and high levels of activation may preferentially recruit aversive circuits. While it is possible that aversive Gr64f-Gal4 -expressing neurons represent off-target cells that do not endogenously express Gr64f, flies naturally avoid sugar in some contexts, such as egg-laying, and subsets of sugar-sensing neurons have been shown to elicit aversion.…”

Section: Discussionmentioning

confidence: 92%

Overlap and divergence of neural circuits mediating distinct behavioral responses to sugar

Jacobs,

Wang,

Lozada-Perdomo

et al. 2023

Preprint

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SUMMARYA single sensory cue can elicit diverse behavioral responses. For example, the taste of sugar robustly promotes feeding1, 2but also influences other behaviors, such as altering locomotor patterns to maximize food-finding3, 4or conferring a rewarding value onto associated contexts or cues.5–7Here, we investigate how sweet taste elicits multiple appetitive behaviors inDrosophila. Are different sugar-evoked behaviors coordinately regulated? At what point does the sugar circuit diverge into different pathways that drive distinct behaviors? We first established an optogenetic paradigm to study the effects of sugar taste on locomotion, spatial preference, and associative learning. We then tested how different sugar-evoked behaviors were modulated by internal and external factors, including hunger, diet, or the presence of an aversive taste. Different behaviors were generally modulated in similar ways, but we also observed some differences that reveal selective modulation of specific behavioral pathways. Finally, we investigated where the sugar taste circuit diverges into different behavioral pathways. A recent study identified a sensory-motor circuit comprising five layers of neurons that drives the initiation of feeding in response to sugar.8By individually manipulating each of these neurons, we show that circuits mediating different innate responses to sugar are partially overlapping and begin to diverge at the level of second- and third-order neurons, whereas circuits for innate versus learned behaviors may diverge at the first synapse. Connectomic analyses reveal distinct subcircuits that mediate different behaviors. Together, these studies provide insight into how neural circuits are organized to elicit diverse behavioral responses to a single stimulus.

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Section: Discussionmentioning

confidence: 92%

Overlap and divergence of neural circuits mediating distinct behavioral responses to sugar

Jacobs,

Wang,

Lozada-Perdomo

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Lines whose names are shown in black font were described in Aso et al, 2014a . Lines from other studies are shown brown font and their sources were as follows: SS01308, Aso et al, 2019 ; G0239, Chiang et al, 2011 ; SS46348, Otto et al, 2020 ; MB618B, SS01127, SS01188, SS01194, SS01298, SS01337, and SS01388, Shuai et al, 2023 release: https://splitgal4.janelia.org . …”

Section: Resultsmentioning

confidence: 99%

New genetic tools for mushroom body output neurons in Drosophila

Rubin,

Aso

2024

eLife

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How memories of past events influence behavior is a key question in neuroscience. The major associative learning center in Drosophila, the Mushroom Body (MB), communicates to the rest of the brain through Mushroom Body Output Neurons (MBONs). While 21 MBON cell types have their dendrites confined to small compartments of the MB lobes, analysis of EM connectomes revealed the presence of an additional 14 MBON cell types that are atypical in having dendritic input both within the MB lobes and in adjacent brain regions. Genetic reagents for manipulating atypical MBONs and experimental data on their functions has been lacking. In this report we describe new cell-type-specific GAL4 drivers for many MBONs, including the majority of atypical MBONs. Using these genetic reagents, we conducted optogenetic activation screening to examine their ability to drive behaviors and learning. These reagents provide important new tools for the study of complex behaviors in Drosophila.

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“…We therefore first focused on γ KC‐to‐MBON‐γ1pedc synaptic transmission. To selectively study these synapses, we expressed red‐shifted channelrhodopsin, CsChrimson (Klapoetke et al., 2014), in a small subset of γ KCs using γ KC‐specific split‐GAL4 driver MB623C (Shuai et al., 2023) together with a stochastic expression system SPARC (Isaacman‐Beck et al., 2020). By using the ‘S’ (or sparse) variant of the SPARC system, we can reliably label a random ∼3%–7% of γ KCs (Isaacman‐Beck et al., 2020), roughly equivalent to the fraction of KCs reliably responsive to a typical odour (Honegger et al., 2011).…”

Section: Resultsmentioning

confidence: 99%

Cyclic nucleotide‐induced bidirectional long‐term synaptic plasticity in Drosophila mushroom body

Yamada,

Davidson,

Hige

2024

The Journal of Physiology

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Activation of the cAMP pathway is one of the common mechanisms underlying long‐term potentiation (LTP). In the Drosophila mushroom body, simultaneous activation of odour‐coding Kenyon cells (KCs) and reinforcement‐coding dopaminergic neurons activates adenylyl cyclase in KC presynaptic terminals, which is believed to trigger synaptic plasticity underlying olfactory associative learning. However, learning induces long‐term depression (LTD) at these synapses, contradicting the universal role of cAMP as a facilitator of transmission. Here, we developed a system to electrophysiologically monitor both short‐term and long‐term synaptic plasticity at KC output synapses and demonstrated that they are indeed an exception in which activation of the cAMP–protein kinase A pathway induces LTD. Contrary to the prevailing model, our cAMP imaging found no evidence for synergistic action of dopamine and KC activity on cAMP synthesis. Furthermore, we found that forskolin‐induced cAMP increase alone was insufficient for plasticity induction; it additionally required simultaneous KC activation to replicate the presynaptic LTD induced by pairing with dopamine. On the other hand, activation of the cGMP pathway paired with KC activation induced slowly developing LTP, proving antagonistic actions of the two second‐messenger pathways predicted by behavioural study. Finally, KC subtype‐specific interrogation of synapses revealed that different KC subtypes exhibit distinct plasticity duration even among synapses on the same postsynaptic neuron. Thus, our work not only revises the role of cAMP in synaptic plasticity by uncovering the unexpected convergence point of the cAMP pathway and neuronal activity, but also establishes the methods to address physiological mechanisms of synaptic plasticity in this important model. imageKey points Although presynaptic cAMP increase generally facilitates synapses, olfactory associative learning in Drosophila, which depends on dopamine and cAMP signalling genes, induces long‐term depression (LTD) at the mushroom body output synapses. By combining electrophysiology, pharmacology and optogenetics, we directly demonstrate that these synapses are an exception where activation of the cAMP–protein kinase A pathway leads to presynaptic LTD. Dopamine‐ or forskolin‐induced cAMP increase alone is not sufficient for LTD induction; neuronal activity, which has been believed to trigger cAMP synthesis in synergy with dopamine input, is required in the downstream pathway of cAMP. In contrast to cAMP, activation of the cGMP pathway paired with neuronal activity induces presynaptic long‐term potentiation, which explains behaviourally observed opposing actions of transmitters co‐released by dopaminergic neurons. Our work not only revises the role of cAMP in synaptic plasticity, but also provides essential methods to address physiological mechanisms of synaptic plasticity in this important model system.

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Driver lines for studying associative learning in Drosophila

Cited by 10 publications

References 146 publications

Overlap and divergence of neural circuits mediating distinct behavioral responses to sugar

Overlap and divergence of neural circuits mediating distinct behavioral responses to sugar

New genetic tools for mushroom body output neurons in Drosophila

Cyclic nucleotide‐induced bidirectional long‐term synaptic plasticity in Drosophila mushroom body

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