Memory-Relevant Mushroom Body Output Synapses Are Cholinergic

Barnstedt, Oliver; Owald, David; Felsenberg, Johannes; Brain, Ruth; Moszynski, John-Paul; Talbot, Clifford B.; Perrat, Paola N.; Waddell, Scott

doi:10.1016/j.neuron.2016.02.015

Cited by 201 publications

(234 citation statements)

References 91 publications

(143 reference statements)

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“…We found that KCs are cholinergic (as in (Barnstedt et al, 2016; Perrat et al, 2013)), the DAL neuron is GABAergic (previously shown by (Chen et al, 2012)), both the MBON-γ5β′2a and MBON-β2β′2a neurons are glutamatergic (consistent with the findings of (Aso et al, 2014b)), and the MBONα3 and V2 neurons are cholinergic (previously shown by (Placais et al, 2013) and (Sejourne et al, 2011)). We detected evidence of potential octopamine synthesis in the MBONα3 neurons and dopamine synthesis in the V2 neurons.…”

Section: Resultssupporting

confidence: 87%

Cell-Type-Specific Transcriptome Analysis in the Drosophila Mushroom Body Reveals Memory-Related Changes in Gene Expression

et al. 2016

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Summary Learning and memory formation in Drosophila rely on a network of neurons in the mushroom bodies (MB). While numerous studies have delineated roles for individual cell types within this network in aspects of learning or memory, whether or not these cells can also be distinguished by the genes they express remains unresolved. In addition, the changes in gene expression that accompany long-term memory formation within the MBs have not yet been studied by neuron type. Here we address both issues by performing RNA sequencing on single cell types (harvested via patch pipets) within the MB. We discover that the expression of genes that encode cell surface receptors is sufficient to identify cell types, and that a subset of these genes, required for sensory transduction in peripheral sensory neurons, are not only expressed within individual neurons of the MB in the central brain, but are also critical for memory formation.

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Section: Resultssupporting

confidence: 87%

Cell-Type-Specific Transcriptome Analysis in the Drosophila Mushroom Body Reveals Memory-Related Changes in Gene Expression

et al. 2016

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“…Data Fig. 7), consistent with findings in the adult that many KCs corelease sNPF peptide with acetylcholine 36 .…”

Section: Cc-by-ncsupporting

confidence: 90%

“…4a-d ever, we found no relationship between the similarity of the PN inputs to KC pairs and the number of KC → KC synapses formed between them (correlation coefficients 0.006 and −0.02 for left and right hemispheres; p > 0.3, comparison to shuffled network). KCs have been shown to be cholinergic in the adult 36 , so it is likely that KC → KC connections are depolarizing. Even when strong dendro-dendritic KC connections are added to our model, dimension only decreases slightly (Fig.…”

Section: Recurrent Kc Interactionsmentioning

confidence: 99%

“…First, we were surprised to observe that the number of KC → MBIN and KC → MBON synapses are comparable. As KCs were shown to be cholinergic in adults 36 , KC → MBIN connections could be potentially depolarizing. Untrained, novel odors can activate DANs in adult Drosophila 47;48 and OANs in bees 3 .…”

Section: A Canonical Circuit In Each Mb Compartment With Unexpected Mmentioning

confidence: 99%

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The complete connectome of a learning and memory center in an insect brain

Eichler

Litwin-Kumar

Feng

et al. 2017

Preprint

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Associating stimuli with positive or negative reinforcement is essential for survival, but a complete wiring diagram of a higherorder circuit supporting associative memory has not been previously available. We reconstructed one such circuit at synaptic resolution, the Drosophila larval mushroom body, and found that most Kenyon cells integrate random combinations of inputs but a subset receives stereotyped inputs from single projection neurons. This organization maximizes performance of a model output neuron on a stimulus discrimination task. We also report a novel canonical circuit in each mushroom body compartment with previously unidentified connections: reciprocal Kenyon cell to modulatory neuron connections, modulatory neuron to output neuron connections, and a surprisingly high number of recurrent connections between Kenyon cells. Stereotyped connections between output neurons could enhance the selection of learned responses. The complete circuit map of the mushroom body should guide future functional studies of this learning and memory center.Massively parallel, higher-order neuronal circuits such as the cerebellum and insect mushroom body serve to form and retain associations between stimuli and reinforcement in vertebrates and higher invertebrates [1][2][3][4][5][6] . Although these systems provide a biological substrate for adaptive behavior, no complete synapseresolution wiring diagram of their connectivity has been available to guide analysis and inspire understanding. The mushroom body (MB) is a higher-order parallel fiber system in many invertebrate brains, including hemimetabolous as well as holometabolous insects and their larval stages 6 . MB function is essential for associative learning in adult insects 1;3-5 and in Drosophila larvae 1;7;8 , from the earliest larval stages onward 9 . Indeed, the basic organization of the adult and the larval MB and their afferent circuits is very similar; however, larvae have about an order of magnitude fewer neurons 7 . Thus, to systematically investigate the organizational logic of the MB, we used serial section electron microscopy (EM) to map with synaptic resolution the complete MB connectome in a first instar Drosophila larva (L1; Fig. 1a). L1 are foraging animals capable of all behaviors previously described in later larval stages 10 , including adaptive behaviors dependent on associative learning 7;9 (Fig. 1b). Their smaller neurons enable fast EM imaging of the entire nervous system and reconstruction of complete circuits 11;12 . Models of sensory processing in many neural circuits feature neurons that fire in response to combinations of sensory inputs, generating a high-dimensional representation of the sensory environment 13 . The intrinsic MB neurons, the Kenyon cells (KCs), integrate in their dendrites inputs from combinations of projection neurons (PNs) that encode various stimuli, predominantly olfactory in both adult 1;4-6 , and larva 12;14 , but also thermal, gustatory

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“…The essentials of the organization of cholinergic neurons in these brain regions are evident in a wide range of vertebrate species from fish to primates (Giraldez-Perez et al, 2013; Hong et al, 2013; Mesulam et al, 1983; Woolf, 1991). Recent studies even find parallels to cholinergic circuits that are essential to memory encoding in invertebrates (Barnstedt et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Basal Forebrain Cholinergic Circuits and Signaling in Cognition and Cognitive Decline

Ballinger

Ananth

Talmage

et al. 2016

Neuron

602

517

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Recent work continues to place cholinergic circuits at center stage for normal executive and mnemonic functioning, and provides compelling evidence that the loss of cholinergic signaling and cognitive decline are inextricably linked. This review focuses on the last few years of studies on the mechanisms by which cholinergic signaling contributes to circuit activity related to cognition. We attempt to identify areas of controversy, as well as consensus, on what is and is not yet known about how cholinergic signaling in the CNS contributes to normal cognitive processes. In addition, we delineate the findings from recent work on the extent to which dysfunction of cholinergic circuits contributes to cognitive decline associated with neurodegenerative disorders.

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Memory-Relevant Mushroom Body Output Synapses Are Cholinergic

Cited by 201 publications

References 91 publications

Cell-Type-Specific Transcriptome Analysis in the Drosophila Mushroom Body Reveals Memory-Related Changes in Gene Expression

Cell-Type-Specific Transcriptome Analysis in the Drosophila Mushroom Body Reveals Memory-Related Changes in Gene Expression

The complete connectome of a learning and memory center in an insect brain

Basal Forebrain Cholinergic Circuits and Signaling in Cognition and Cognitive Decline

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