Interactive nanocluster compaction of the ELKS scaffold and Cacophony Ca ²⁺ channels drives sustained active zone potentiation

Science Advances, Год журнала: 2023, Номер 9(7)

Опубликована: Фев. 17, 2023

At presynaptic active zones (AZs), conserved scaffold protein architectures control synaptic vesicle (SV) release by defining the nanoscale distribution and density of voltage-gated Ca 2+ channels (VGCCs). While AZs can potentiate SV in minutes range, we lack an understanding how AZ components VGCCs engage into potentiation. We here establish dynamic, intravital single-molecule imaging endogenously tagged proteins at Drosophila undergoing homeostatic During potentiation, numbers α1 VGCC subunit Cacophony (Cac) increased per AZ, while their mobility decreased compacted. These dynamic Cac changes depended on interaction between channel’s intracellular carboxyl terminus membrane-close amino-terminal region ELKS-family Bruchpilot, whose compacted drastically. The Cac-ELKS/Bruchpilot was also needed for sustained Our analysis illustrates couples to dynamics a state

Язык: Английский

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Distinct input-specific mechanisms enable presynaptic homeostatic plasticity

Science Advances, Год журнала: 2025, Номер 11(7)

Опубликована: Фев. 14, 2025

Synapses are endowed with the flexibility to change through experience, but must be sufficiently stable last a lifetime. This tension is illustrated at Drosophila neuromuscular junction (NMJ), where two motor inputs that differ in structural and functional properties coinnervate most muscles coordinate locomotion. To stabilize NMJ activity, neurons augment neurotransmitter release following diminished postsynaptic glutamate receptor functionality, termed presynaptic homeostatic potentiation (PHP). How these distinct contribute PHP plasticity remains enigmatic. We have used botulinum neurotoxin selectively silence each input resolve their roles PHP, demonstrating specific: Chronic (genetic) targets tonic MN-Ib, active zone remodeling enhances Ca 2+ influx promote increased release. In contrast, acute (pharmacological) increases vesicle pools potentiate phasic MN-Is. Thus, modulations nanoarchitecture, pools, collaborate enable input-specific expression.

Язык: Английский

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Mechanistic insights into cAMP-mediated presynaptic potentiation at hippocampal mossy fiber synapses

Frontiers in Cellular Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Июль 13, 2023

Presynaptic plasticity is an activity-dependent change in the neurotransmitter release and plays a key role dynamic modulation of synaptic strength. Particularly, presynaptic potentiation mediated by cyclic adenosine monophosphate (cAMP) widely seen across animals thought to contribute learning memory. Hippocampal mossy fiber-CA3 pyramidal cell synapses have been used as model because robust short- long-term forms. Moreover, direct recordings from large fiber terminals allow one dissect mechanisms. Recently, super-resolution microscopy flash-and-freeze electron revealed localizations site molecules vesicles during at nanoscale, identifying molecular mechanisms potentiation. Incorporating these growing knowledges, we try present plausible underlying cAMP-mediated

Язык: Английский

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Blobby is a synaptic active zone assembly protein required for memory in Drosophila

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 2, 2025

Abstract At presynaptic active zones (AZs), scaffold proteins are critical for coordinating synaptic vesicle release and forming essential nanoarchitectures. However, regulatory principles steering AZ assembly, function, plasticity remain insufficiently understood. We here identify an additional Drosophila protein, “Blobby”, proper nano-organization. Blobby biochemically associates with the ELKS family protein Bruchpilot (BRP) integrates into newly AZs. Loss of results in fewer AZs forming, ectopic accumulations (“blobs”) disrupts nanoscale architecture BRP-AZ scaffold. Functionally, blobby mutants show diminished evoked currents due to reduced probability functional sites. is also present adult brain synapses, post-developmental knockdown mushroom body impairs olfactory aversive memory consolidation. Thus, our analysis identifies layer regulation developmental assembly but AZ-mediated controlling behavior.

Язык: Английский

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Dopamine-Dependent Plasticity Is Heterogeneously Expressed by Presynaptic Calcium Activity across Individual Boutons of theDrosophilaMushroom Body

eNeuro, Год журнала: 2023, Номер 10(10), С. ENEURO.0275 - 23.2023

Опубликована: Окт. 1, 2023

The

Язык: Английский

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Skewing information flow through pre- and postsynaptic plasticity in the mushroom bodies ofDrosophila

Learning & Memory, Год журнала: 2024, Номер 31(5), С. a053919 - a053919

Опубликована: Май 1, 2024

Animal brains need to store information construct a representation of their environment. Knowledge what happened in the past allows both vertebrates and invertebrates predict future outcomes by recalling previous experience. Although invertebrate vertebrate share common principles at molecular, cellular, circuit-architectural levels, there are also obvious differences as exemplified use acetylcholine versus glutamate considered main excitatory neurotransmitters respective central nervous systems. Nonetheless, across systems, synaptic plasticity is thought be substrate for memory storage. Therefore, how brain circuits contacts change following learning fundamental interest understanding computations tied behavior any animal. Recent progress has been made such plastic changes olfactory associative mushroom bodies (MBs) Drosophila . A current framework memory-guided behavioral selection based on MB skew model, which antagonistic pathways selectively changed strength. Here, we review insights into dedicated output update known about pre- postsynaptic compartments neurons.

Язык: Английский

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An antagonism between Spinophilin and Syd-1 operates upstream of memory-promoting presynaptic long-term plasticity

eLife, Год журнала: 2023, Номер 12

Опубликована: Сен. 28, 2023

We still face fundamental gaps in understanding how molecular plastic changes of synapses intersect with circuit operation to define behavioral states. Here, we show that an antagonism between two conserved regulatory proteins, Spinophilin (Spn) and Syd-1, controls presynaptic long-term plasticity the maintenance olfactory memories Drosophila. While Spn mutants could not trigger nanoscopic active zone remodeling under homeostatic challenge failed stably potentiate neurotransmitter release, concomitant reduction Syd-1 rescued all these deficits. The Spn/Syd-1 converged on close F-actin, genetic or acute pharmacological depolymerization F-actin deficits by allowing access synaptic vesicle release sites. Within intrinsic mushroom body neurons, specifically controlled memory stabilization but initial learning. Thus, this evolutionarily protein complex behaviorally relevant plasticity, also observed mammalian brain enigmatic concerning its mechanisms relevance.

Язык: Английский

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Presynaptic regulators in memory formation

Learning & Memory, Год журнала: 2024, Номер 31(5), С. a054013 - a054013

Опубликована: Май 1, 2024

The intricate molecular and structural sequences guiding the formation consolidation of memories within neuronal circuits remain largely elusive. In this study, we investigate roles two pivotal presynaptic regulators, small GTPase Rab3, enriched at synaptic vesicles, cell adhesion protein Neurexin-1, in distinct memory phases Drosophila mushroom body Kenyon cells. Our findings suggest that both proteins play crucial memory-supporting processes terminal, operating plasticity modules. These modules likely encompass remodeling maturation existing active zones (AZs), as well new AZs.

Язык: Английский

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The structure and assembly of the hetero-octameric BLOC-one-related complex

Structure, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Язык: Английский

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A subset of cholinergic mushroom body neurons blocks long-term memory formation in Drosophila

Cell Reports, Год журнала: 2023, Номер 42(8), С. 112974 - 112974

Опубликована: Авг. 1, 2023

Long-term memory (LTM) requires learning-induced synthesis of new proteins allocated to specific neurons and synapses in a neural circuit. Not all learned information, however, becomes permanent memory. How the brain gates relevant information into LTM remains unclear. In Drosophila adults, weak learning after single training session an olfactory aversive task typically does not induce protein-synthesis-dependent LTM. Instead, strong multiple spaced sessions is required. Here, we report that pre-synaptic active-zone protein cholinergic signaling from early α/β subset mushroom body (MB) produce downstream inhibitory effect on formation. When eliminated these neurons, was then sufficient form This bidirectional circuit mechanism modulates transition between distinct phase functions different subpopulations MB

Язык: Английский

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