A connectome of a learning and memory center in the adult Drosophila brain

Takemura, Shin-ya; Aso, Yoshinori; Hige, Toshihide; Wong, Allan; Lǚ, Zhiyuan; Xu, Chengpei; Rivlin, Patricia K.; Hess, Harald F.; Zhao, Ting; Parag, Toufiq; Berg, Stuart; Huang, Gary B.; Katz, William T.; Olbris, Donald J.; Plaza, Stephen M.; Umayam, Lowell; Aniceto, Roxanne; Chang, Lei-Ann; Lauchie, Shirley; Ogundeyi, Omotara; Ordish, Christopher; Shinomiya, Aya; Sigmund, Christopher; Takemura, Satoko; Tran, Julie; Turner, Glenn; Rubin, Gerald M.; Scheffer, Louis K

doi:10.7554/elife.26975

Cited by 356 publications

(525 citation statements)

References 148 publications

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“…8). This suggests that MBINs may have two concurrent modes of action onto KCs and MBONs: activation via synaptic release (of dopamine, octopamine, or fast neurotransmitters 39 ) and neuromodulation via volume release. These two modes, coupled with the diverse connection types among KCs, MBINs, and MBONs, may provide a powerful and flexible substrate for associative learning.…”

Section: Resultsmentioning

confidence: 99%

“…Even though individual neurons may change through metamorphosis, many of the basic aspects of the MB architecture are shared between larval and adult Drosophila stages and with other insects (see Supplementary Tables 6 and 7) 1,3–6,8,18,39,40 . We therefore expect that the circuit motifs identified here are not unique to the L1 developmental stage, but instead represent a general feature of Drosophila and insect MBs.…”

Section: Discussionmentioning

confidence: 99%

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

Eichler

Litwin-Kumar

et al. 2017

Nature

481

726

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Associating stimuli with positive or negative reinforcement is essential for survival, but a complete wiring diagram of a higher-order circuit supporting associative memory has not been previously available. Here we reconstruct one such circuit at synaptic resolution, the Drosophila larval mushroom body. We find that most Kenyon cells integrate random combinations of inputs but that 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 found between output neurons could enhance the selection of learned behaviours. The complete circuit map of the mushroom body should guide future functional studies of this learning and memory centre.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Eichler

Litwin-Kumar

et al. 2017

Nature

481

726

View full text Add to dashboard Cite

show abstract

“…Given that the DAn synapse with MBn axons and MBOn dendrites and DA receptors reside in both compartments (Takemura et al, 2017; Hattori et al, 2017; Crocker et al, 2016), both sides of the synapse are probably modulated. However, many of the molecules required for normal memory formation and forgetting are expressed and required in MBns, including adenylyl cyclase (Mao et al, 2004), dDA1 (Qin et al, 2012), Gαs (Connolly et al, 1996), Rac1 (Shuai et al, 2010), Scribble (Cervantes-Sandoval et al, 2016), and Gαq (Himmelreich et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Dopamine Neurons Mediate Learning and Forgetting through Bidirectional Modulation of a Memory Trace

2018

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SUMMARY It remains unclear how memory engrams are altered by experience, such as new learning, to cause forgetting. Here, we report that short-term aversive memory in Drosophila is encoded by and retrieved from the mushroom body output neuron MBOn-γ2αʹ1. Pairing an odor with aversive electric shock creates a robust depression in the calcium response of MBOn-γ2αʹ1 and increases avoidance to the paired odor. Electric shock after learning, which activates the cognate dopamine neuron DAn-γ2αʹ1, restores the response properties of MBOn-γ2αʹ1 and causes behavioral forgetting. Conditioning with a second odor restores the responses of MBOn-γ2αʹ1 to a previously learned odor while depressing responses to the newly learned odor, showing that learning and forgetting can occur simultaneously. Moreover, optogenetic activation of DAn-γ2αʹ1 is sufficient for the bidirectional modulation of MBOn-γ2αʹ1 response properties. Thus, a single DAn can drive both learning and forgetting by bidirectionally modulating a cellular memory trace.

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“…Electron microscopy has been used recently to systematically reconstruct both the AL (Berck et al, 2016) and downstream integrative centers mediating olfactory learning and memory processes (Takemura et al, 2017). In these studies, the electron-dense AZ scaffold (“T bar”) was used as the crucial landmark to identify AZs and, consequently, synaptic connections between reconstructed neurons.…”

Section: Discussionmentioning

confidence: 99%

Active Zone Scaffold Protein Ratios Tune Functional Diversity across Brain Synapses

et al. 2018

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High-throughput electron microscopy has started to reveal synaptic connectivity maps of single circuits and whole brain regions, for example, in the Drosophila olfactory system. However, efficacy, timing, and frequency tuning of synaptic vesicle release are also highly diversified across brain synapses. These features critically depend on the nanometer-scale coupling distance between voltage-gated Ca channels (VGCCs) and the synaptic vesicle release machinery. Combining light super resolution microscopy with in vivo electrophysiology, we show here that two orthogonal scaffold proteins (ELKS family Bruchpilot, BRP, and Syd-1) cluster-specific (M)Unc13 release factor isoforms either close (BRP/Unc13A) or further away (Syd-1/Unc13B) from VGCCs across synapses of the Drosophila olfactory system, resulting in different synapse-characteristic forms of short-term plasticity. Moreover, BRP/Unc13A versus Syd-1/Unc13B ratios were different between synapse types. Thus, variation in tightly versus loosely coupled scaffold protein/(M)Unc13 modules can tune synapse-type-specific release features, and "nanoscopic molecular fingerprints" might identify synapses with specific temporal features.

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A connectome of a learning and memory center in the adult Drosophila brain

Cited by 356 publications

References 148 publications

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

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

Dopamine Neurons Mediate Learning and Forgetting through Bidirectional Modulation of a Memory Trace

Active Zone Scaffold Protein Ratios Tune Functional Diversity across Brain Synapses

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