Compensatory variability in network parameters enhances memory performance in the
            <i>Drosophila</i>
            mushroom body

Abdelrahman, Nada Y.; Vasilaki, Eleni; Lin, Andrew C.

doi:10.1073/pnas.2102158118

Cited by 9 publications

(9 citation statements)

References 71 publications

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“…Such a model is supported by a recent computational study demonstrating that variability in parameters controlling neuronal excitability of individual KCs negatively affects associative memory performance. The authors provide evidence that compensatory variation mechanisms exist that ensure similar activity levels between all odor-encoding KC sets to maintain efficient memory performance ( Abdelrahman et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

The cellular architecture of memory modules in Drosophila supports stochastic input integration

Hafez

Escribano

Ziegler

et al. 2023

eLife

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The ability to associate neutral stimuli with valence information and to store these associations as memories forms the basis for decision making. To determine the underlying computational principles, we build a realistic computational model of a central decision module within the Drosophila mushroom body (MB), the fly's center for learning and memory. Our model combines the electron microscopy-based architecture of one MB output neuron (MBON-α3), the synaptic connectivity of its 948 presynaptic Kenyon cells (KCs), and its membrane properties obtained from patch-clamp recordings. We show that this neuron is electrotonically compact and that synaptic input corresponding to simulated odor input robustly drives its spiking behavior. Therefore, sparse innervation by KCs can efficiently control and modulate MBON activity in response to learning with minimal requirements on the specificity of synaptic localization. This architecture allows efficient storage of large numbers of memories using the flexible stochastic connectivity of the circuit.

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Section: Discussionmentioning

confidence: 99%

The cellular architecture of memory modules in Drosophila supports stochastic input integration

Hafez

Escribano

Ziegler

et al. 2023

eLife

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“…The same question is waiting to be addressed for other neuromodulators as well, such as DPM-derived serotonin that may extend dopamine’s functional plasticity window within the KC axon ( Zeng et al, 2023 ). Such investigation will also be of value for future modeling studies, which to this point must assume simple spiking of KCs and equal or random weights to KC-to-MBON synapses ( Smith et al, 2008 ; Huerta and Nowotny, 2009 ; Peng and Chittka, 2017 ; Abdelrahman et al, 2021 ; Hafez et al, 2023 ). The intersection of these approaches will be especially important for understanding the subcellular mechanisms of learning-related processes, particularly as they appear to be distributed across functional units, whether they be compartmentalized axon bundles or boutons along an individual axon.…”

Section: Discussionmentioning

confidence: 99%

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

Davidson,

Kaushik,

Hige

2023

eNeuro

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TheDrosophilamushroom body (MB) is an important model system for studying the synaptic mechanisms of associative learning. In this system, coincidence of odor-evoked calcium influx and dopaminergic input in the presynaptic terminals of Kenyon cells (KCs), the principal neurons of the MB, triggers long-term depression (LTD), which plays a critical role in olfactory learning. However, it is controversial whether such synaptic plasticity is accompanied by a corresponding decrease in odor-evoked calcium activity in the KC presynaptic terminals. Here, we address this question by inducing LTD by pairing odor presentation with optogenetic activation of dopaminergic neurons (DANs). This allows us to rigorously compare the changes at the pre- and postsynaptic sites in the same conditions. By imaging presynaptic acetylcholine release in the condition where LTD is reliably observed in the postsynaptic calcium signals, we show that neurotransmitter release from KCs is depressed selectively in the MB compartments innervated by activated DANs, demonstrating the presynaptic nature of LTD. However, total odor-evoked calcium activity of the KC axon bundles does not show concurrent depression. We further conduct calcium imaging in individual presynaptic boutons and uncover the highly heterogeneous nature of calcium plasticity. Namely, only a subset of boutons, which are strongly activated by associated odors, undergo calcium activity depression, while weakly responding boutons show potentiation. Thus, our results suggest an unexpected nonlinear relationship between presynaptic calcium influx and the results of plasticity, challenging the simple view of cooperative actions of presynaptic calcium and dopaminergic input.Significance StatementDopamine-induced long-term synaptic depression in the mushroom body is a key mechanism of olfactory associative learning inDrosophila. Although multiple lines of evidence indicate the presynaptic origin of this plasticity, it has been controversial whether and how the plasticity affects odor-evoked presynaptic calcium influx. Here, we demonstrate that the plasticity of presynaptic calcium signals is highly heterogeneous across individual presynaptic boutons, even among those on the same, likely spiking axons. The mode of plasticity (i.e., potentiation or depression) depends on the original response size. These results challenge the simple view that coincidence of presynaptic calcium and dopaminergic input triggers depression and suggest the plasticity outcome is finely controlled by the activity of individual synapses and local neuromodulatory signals.

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“…Importantly, by comparing the CS+ and CS- responses to those of untrained odors, we ascribed plasticity to potentiation or depression (accounting for any non-associative olfactory adaptation) within each compartment. This is relevant for modeling efforts, where it has been unclear whether to include potentiation (along with depression) in the learning rule(s) at KC-MBON synapses ( Abdelrahman et al, 2021 ; Bennett et al, 2021 ; Jiang and Litwin-Kumar, 2021 ; Springer and Nawrot, 2021 ). In addition, the experiments revealed an additional layer of spatial regulation in the γ1–γ3 compartments: a gradient of CS+ potentiation to CS- depression following appetitive conditioning.…”

Section: Discussionmentioning

confidence: 99%

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

Stahl

Noyes

Boto

et al. 2022

eLife

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Anatomical and physiological compartmentalization of neurons is a mechanism to increase the computational capacity of a circuit, and a major question is what role axonal compartmentalization plays. Axonal compartmentalization may enable localized, presynaptic plasticity to alter neuronal output in a flexible, experience-dependent manner. Here we show that olfactory learning generates compartmentalized, bidirectional plasticity of acetylcholine release that varies across the longitudinal compartments of Drosophila mushroom body (MB) axons. The directionality of the learning-induced plasticity depends on the valence of the learning event (aversive vs. appetitive), varies linearly across proximal to distal compartments following appetitive conditioning, and correlates with learning-induced changes in downstream mushroom body output neurons (MBONs) that modulate behavioral action selection. Potentiation of acetylcholine release was dependent on the CaV2.1 calcium channel subunit cacophony. In addition, contrast between the positive conditioned stimulus and other odors required the inositol triphosphate receptor (IP3R), which maintained responsivity to odors upon repeated presentations, preventing adaptation. Downstream from the mushroom body, a set of MBONs that receive their input from the g3 MB compartment were required for normal appetitive learning, suggesting that they represent a key node through which reward learning influences decision-making. These data demonstrate that learning drives valence-correlated, compartmentalized, bidirectional potentiation and depression of synaptic neurotransmitter release, which rely on distinct mechanisms and are distributed across axonal compartments in a learning circuit.

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Compensatory variability in network parameters enhances memory performance in the Drosophila mushroom body

Cited by 9 publications

References 71 publications

The cellular architecture of memory modules in Drosophila supports stochastic input integration

The cellular architecture of memory modules in Drosophila supports stochastic input integration

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

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

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