Local 5-HT signaling bi-directionally regulates the coincidence time window for associative learning

Neuron, Год журнала: 2023, Номер 111(7), С. 1118 - 1135.e5

Опубликована: Янв. 26, 2023

Язык: Английский

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Associative learning drives longitudinally graded presynaptic plasticity of neurotransmitter release along axonal compartments

eLife, Год журнала: 2022, Номер 11

Опубликована: Март 14, 2022

Anatomical and physiological compartmentalization of neurons is a mechanism to increase the computational capacity circuit, major question what role axonal plays. Axonal may enable localized, presynaptic plasticity alter neuronal output in flexible, experience-dependent manner. Here, we show that olfactory learning generates compartmentalized, bidirectional acetylcholine release varies across longitudinal compartments Drosophila mushroom body (MB) axons. The directionality learning-induced depends on valence event (aversive vs. appetitive), linearly proximal distal following appetitive conditioning, correlates with changes downstream (MBONs) modulate behavioral action selection. Potentiation was dependent Ca V 2.1 calcium channel subunit cacophony . In addition, contrast between positive conditioned stimulus other odors required inositol triphosphate receptor, which maintained responsivity upon repeated presentations, preventing adaptation. Downstream from MB, set MBONs receive their input γ3 MB compartment were for normal learning, suggesting they represent key node through reward influences decision-making. These data demonstrate drives valence-correlated, potentiation, depression synaptic neurotransmitter release, rely distinct mechanisms are distributed circuit.

Язык: Английский

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Genetically Encoded Sensors for the In Vivo Detection of Neurochemical Dynamics

Annual Review of Analytical Chemistry, Год журнала: 2024, Номер 17(1), С. 367 - 392

Опубликована: Июль 17, 2024

The ability to measure dynamic changes in neurochemicals with high spatiotemporal resolution is essential for understanding the diverse range of functions mediated by brain. We review recent advances genetically encoded sensors detecting and discuss their vivo applications. For example, notable progress has been made respect second messengers such as cyclic adenosine monophosphate, enabling real-time monitoring these at single-cell even subcellular resolution. Moreover, emergence highly sensitive neurotransmitters neuromodulators greatly accelerated study signaling molecules a wide variety behavioral models using an array powerful imaging techniques. Finally, we future direction neurochemical sensors, including concentrations potential multiplex imaging.

Язык: Английский

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The caloric value of food intake structurally adjusts a neuronal mushroom body circuit mediating olfactory learning inDrosophila

Learning & Memory, Год журнала: 2024, Номер 31(5), С. a053997 - a053997

Опубликована: Май 1, 2024

Associative learning enables the adaptive adjustment of behavioral decisions based on acquired, predicted outcomes. The valence what is learned influenced not only by stimuli and their temporal relations, but also prior experiences internal states. In this study, we used fruit fly Drosophila melanogaster to demonstrate that neuronal circuits involved in associative olfactory undergo restructuring during extended periods low-caloric food intake. Specifically, observed a decrease connections between specific dopaminergic neurons (DANs) Kenyon cells at distinct compartments mushroom body. This structural synaptic plasticity was contingent upon presence allatostatin A receptors DANs could be mimicked optogenetically expressing light-activated adenylate cyclase exactly these DANs. Importantly, found rearrangement aversive, punishment-induced did impact appetitive, reward-based learning. Whether induced prolonged conditions or optogenetic manipulation cAMP levels, resulted reduction aversive Consequently, balance positive negative reinforcing signals shifted, diminishing ability learn avoid odor cues signaling These results exemplify how circuit required for memory undergoes dependent nutritional value food.

Язык: Английский

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Postsynaptic plasticity of cholinergic synapses underlies the induction and expression of appetitive and familiarity memories in Drosophila

eLife, Год журнала: 2022, Номер 11

Опубликована: Окт. 17, 2022

In vertebrates, several forms of memory-relevant synaptic plasticity involve postsynaptic rearrangements glutamate receptors. contrast, previous work indicates that Drosophila and other invertebrates store memories using presynaptic cholinergic synapses. Here, we provide evidence for at output synapses from the mushroom bodies (MBs). We find nicotinic acetylcholine receptor (nAChR) subunit α5 is required within specific MB neurons appetitive memory induction but dispensable aversive memories. addition, nAChR α2 subunits mediate expression likely function downstream scaffold protein discs large (Dlg). show traces can be induced independently presynapse, in vivo dynamics are changed both context associative non-associative (familiarity) formation, underlying different rules. Therefore, regardless neurotransmitter identity, key principles support storage across phyla.

Язык: Английский

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Regulation of presynaptic Ca2+ channel abundance at active zones through a balance of delivery and turnover

eLife, Год журнала: 2022, Номер 11

Опубликована: Июль 14, 2022

Voltage-gated Ca2+ channels (VGCCs) mediate influx to trigger neurotransmitter release at specialized presynaptic sites termed active zones (AZs). The abundance of VGCCs AZs regulates probability (Pr), a key determinant synaptic strength. Although biosynthesis, delivery, and recycling cooperate establish AZ VGCC abundance, experimentally isolating these distinct regulatory processes has been difficult. Here, we describe how the levels cacophony (Cac), sole VGCC-mediating transmission in Drosophila, are determined. We also analyzed relationship between Cac, conserved subunit α2δ, core scaffold protein Bruchpilot (BRP) establishing functional AZ. find that Cac BRP independently regulated growing AZs, as is dispensable for formation structural maturation, not limiting accumulation. Additionally, stop accumulating after an initial growth phase, whereas continue increase given extended developmental time. buffered against moderate increases or decreases lacks this buffering. To probe mechanisms determine intravital FRAP photoconversion were used separately measure delivery turnover individual over multi-day period. occurs broadly across population, correlates with size, rate-limited by α2δ. does undergo significant lateral transfer neighboring course development, removal from occur promoted new generating cap on accumulation mature AZs. Together, findings reveal set throughout synapse development maintenance.

Язык: Английский

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Innate and learned odor-guided behaviors utilize distinct molecular signaling pathways in a shared dopaminergic circuit

Cell Reports, Год журнала: 2023, Номер 42(2), С. 112026 - 112026

Опубликована: Янв. 25, 2023

Odor-based learning and innate odor-driven behavior have been hypothesized to require separate neuronal circuitry. Contrary this notion, olfactory were recently shown share circuitry that includes the Drosophila mushroom body (MB). But how a single circuit drives two discrete behaviors remains unknown. Here, we define an MB responsible for both odor avoidance distinct dDA1 dopamine receptor-dependent signaling pathways mediate these behaviors. Associative learning-induced plasticity rutabaga-encoded adenylyl cyclase activity in MB. In contrast, preferences driven by naive neurotransmission are rutabaga independent, requiring ACXD. Both converge on PKA downstream MBON-γ2α'1. Importantly, utilization of shared only becomes apparent with hunger, indicating hardwired more flexible during states stress.

Язык: Английский

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Spontaneous recovery of reward memory through active forgetting of extinction memory

Current Biology, Год журнала: 2023, Номер 33(5), С. 838 - 848.e3

Опубликована: Фев. 1, 2023

Язык: Английский

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Mechanisms controlling the trafficking, localization, and abundance of presynaptic Ca2+ channels

Frontiers in Molecular Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Янв. 13, 2023

Voltage-gated Ca 2+ channels (VGCCs) mediate influx to trigger neurotransmitter release at specialized presynaptic sites termed active zones (AZs). The abundance of VGCCs AZs regulates probability ( P r ), a key determinant synaptic strength. Given this functional significance, defining the processes that cooperate establish AZ VGCC is critical for understanding how these mechanisms set strength and they might be regulated control plasticity. involves multiple steps, including channel biosynthesis (transcription, translation, trafficking through endomembrane system), forward axonal delivery terminals, incorporation retention sites, protein recycling. Here we discuss synapses, highlighting findings from invertebrate vertebrate models.

Язык: Английский

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Synaptic enrichment and dynamic regulation of the two opposing dopamine receptors within the same neurons

Опубликована: Янв. 20, 2025

Dopamine can play opposing physiological roles depending on the receptor subtype. In fruit fly Drosophila melanogaster , Dop1R1 and Dop2R encode D 1 - 2 -like receptors, respectively, are reported to oppositely regulate intracellular cAMP levels. Here, we profiled expression subcellular localization of endogenous in specific cell types mushroom body circuit. For cell-type-specific visualization proteins, employed reconstitution split-GFP tagged proteins. We detected dopamine receptors at both presynaptic postsynaptic sites multiple types. Quantitative analysis revealed enrichment sites, with showing a greater degree than Dop1R1. The neurons suggests dual feedback regulation as autoreceptors. Furthermore, discovered starvation-dependent, bidirectional modulation PAM PPL1 clusters, two distinct subsets neurons, suggesting appetitive behaviors. Our results highlight significance co-expression spatial conditional responses neurons.

Язык: Английский

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