Locomotor and olfactory responses in dopamine neurons of the Drosophila superior-lateral brain

Marquis, Michael; Wilson, Rachel I.

doi:10.1016/j.cub.2022.11.008

Cited by 8 publications

(7 citation statements)

References 74 publications

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“…Finally, the dopaminergic internal feedback from the LAL – necessary to categorise learning into different MB lobes compartments – also predicts a strong link between locomotion and activity in the MB, with rapid shifts of dopaminergic activity across the MB lobes as the insects is moving in the world. This corroborates recent observations in drosophila that dopamine release in the brain strongly correlates with the animals’ movements 58,82 , and indeed, shifts dynamically across the MBs lobes 57,83 . Overall, this supports the view that the MBs provide an active coding that operates in a tight closed-loop with the ongoing behaviour.…”

Section: Discussionsupporting

confidence: 91%

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Neurons from pre-motor areas to the Mushroom bodies can orchestrate latent visual learning in navigating insects

Wystrach

2023

Preprint

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Spatial learning is peculiar. It can occur continuously and stimuli of the world need to be encoded according to some spatial organisation. Recent evidence showed that insects categorise visual memories as whether their gaze is facing left vs. right from their goal, but how such categorisation is achieved during learning remains unknown. Here we analysed the movements of ants exploring the world around their nest, and used a biologically constrained neural model to show that such parallel, lateralized visual memories can be acquired straightforwardly and continuously as the agent explore the world. During learning, left and right visual memories can be formed in different neural comportments (of the mushroom bodies lobes) through existing lateralised dopaminergic neural feedback from pre-motor areas (the lateral accessory lobes) receiving output from path integration (in the central complex). As a result, path integration organises visual learning internally, without the need to be expressed through behaviour; and therefore, views can be learnt continuously (without suffering memory overload) while the insect is free to explore the world randomly or using any other navigational mechanism. After learning, this circuit produces robust homing performance in a 3D reconstructed natural habitat despite a noisy visual recognition performance. Overall this illustrates how continuous bidirectional relationships between pre-motor areas and visual memory centres can orchestrate latent spatial learning and produce efficient navigation behaviour.

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Section: Discussionsupporting

confidence: 91%

“…Note that other neural candidates could equally achieve the desired LAL-to-MBs learning signals, albeit indirectly. For instance, some feedback from pre-motor areas modulate dopaminergic neurons that in turn, trigger synaptic modulation in the MBs lobes 57,58 .…”

Section: Ants Look In All Directions During Learning Walksmentioning

confidence: 99%

Neurons from pre-motor areas to the Mushroom bodies can orchestrate latent visual learning in navigating insects

Wystrach

2023

Preprint

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“…We found similarities between Parkin and Dop1R mutant flies in their altered responses to predator-mimicking passing shadows: reduced walking speed and decreased overall reactivity, suggesting that the lack of dopamine action through Dop1R may be one of the common pathways underlying motor deficits. This is in line with a recent study demonstrating impaired startle-induced geotaxis and locomotor reactivity in Dop1R mutant flies (Sun et al, 2018), similar to what had been shown for Parkin flies (Aggarwal et al, 2019), and a demonstration of dopaminergic control over walking speed (Marquis and Wilson, 2022). In contrast, flies expressing human α-syn showed moderate changes in motor behavior except for a marked prolongation of freezing duration upon threating stimuli.…”

Section: Discussionsupporting

confidence: 91%

Altered reactivity to threatening stimuli inDrosophilamodels of Parkinson’s disease, revealed by a trial-based assay

Kajtor,

Billes,

Király

et al. 2023

Preprint

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The fruit fly Drosophila melanogaster emerges as an affordable, genetically tractable model of behavior and brain diseases. However, despite the surprising level of evolutionary conservation from flies to humans, significant genetic and circuit-level differences hinder the interpretability of fruit fly models for human disease. Therefore, to facilitate fly-to-human translation with more direct behavior-level comparison, we surveyed the rarely-exploited, rich behavioral repertoire of fruit flies with genetic alterations relevant to Parkinson's disease (PD). Flies displayed variable behaviors, including freezing, slowing and running, in response to predator-mimicking passing shadows used as threatening stimuli in a single-animal trial-based assay. We found that the expression of human mutant Parkin in flies resulted in reduced walking speed and decreased reactivity to passing shadows. Flies with dopamine receptor mutations showed similar alterations, consistent with the motor and cognitive deficits typical in humans with PD. However, Drosophila overexpressing the human form of α-synuclein manifested in only moderate phenotypical alterations, suggesting that other fruit fly models may be favored in PD research. We also found age-dependent trends in behavioral choice across the fly lifespan, while dopamine receptor mutant flies maintained their decreased general reactivity throughout all age groups. Our data demonstrate that single-trial behavioral analysis can reveal subtle behavioral changes in mutant flies that can be used to further our understanding of disease pathomechanisms and help gauge the validity of genetic Drosophila models of neurodegeneration.

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“…Our data also firmly support this observation because dopamine induced as large a cAMP increase as forskolin. Moreover, DAN activity is strongly modulated by the animal's instantaneous locomotion (Cohn et al., 2015; Marquis & Wilson, 2022; Siju et al., 2020; Zolin et al., 2021). Thus, the resulting ‘aberrant’ fluctuation of the cAMP level may prevent it from being a faithful biochemical reporter of coincidence.…”

Section: Discussionmentioning

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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Locomotor and olfactory responses in dopamine neurons of the Drosophila superior-lateral brain

Cited by 8 publications

References 74 publications

Neurons from pre-motor areas to the Mushroom bodies can orchestrate latent visual learning in navigating insects

Neurons from pre-motor areas to the Mushroom bodies can orchestrate latent visual learning in navigating insects

Altered reactivity to threatening stimuli inDrosophilamodels of Parkinson’s disease, revealed by a trial-based assay

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

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