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Mushroom body output neurons encode valence and guide memory-based action selection in Drosophila.

Aso Y, Sitaraman D, Ichinose T, Kaun KR, Vogt K, Belliart-Guérin G, Plaçais PY, Robie AA, Yamagata N, Schnaitmann C, Rowell WJ, Johnston RM, Ngo TT, Chen N, Korff W, Nitabach MN, Heberlein U, Preat T, Branson KM, Tanimoto H, Rubin GM - Elife (2014)

Bottom Line: The behavioral effects of MBON perturbation are combinatorial, suggesting that the MBON ensemble collectively represents valence.We propose that local, stimulus-specific dopaminergic modulation selectively alters the balance within the MBON network for those stimuli.Our results suggest that valence encoded by the MBON ensemble biases memory-based action selection.

View Article: PubMed Central - PubMed

Affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.

ABSTRACT
Animals discriminate stimuli, learn their predictive value and use this knowledge to modify their behavior. In Drosophila, the mushroom body (MB) plays a key role in these processes. Sensory stimuli are sparsely represented by ∼2000 Kenyon cells, which converge onto 34 output neurons (MBONs) of 21 types. We studied the role of MBONs in several associative learning tasks and in sleep regulation, revealing the extent to which information flow is segregated into distinct channels and suggesting possible roles for the multi-layered MBON network. We also show that optogenetic activation of MBONs can, depending on cell type, induce repulsion or attraction in flies. The behavioral effects of MBON perturbation are combinatorial, suggesting that the MBON ensemble collectively represents valence. We propose that local, stimulus-specific dopaminergic modulation selectively alters the balance within the MBON network for those stimuli. Our results suggest that valence encoded by the MBON ensemble biases memory-based action selection.

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Expression patterns of split-GAL4s that caused odor-ethanol intoxication memory phenotypes.(A–I) Expression patterns of selected split-GAL4 drivers as assessed with pJFRC2-10XUAS-IVS-mCD8::GFP (VK00005). Full confocal stacks of these images are available at www.janelia.org/split-gal4. (J) Confocal image of a single brain hemisphere of MB018B for the MBON-α′2.DOI:http://dx.doi.org/10.7554/eLife.04580.028
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fig11s1: Expression patterns of split-GAL4s that caused odor-ethanol intoxication memory phenotypes.(A–I) Expression patterns of selected split-GAL4 drivers as assessed with pJFRC2-10XUAS-IVS-mCD8::GFP (VK00005). Full confocal stacks of these images are available at www.janelia.org/split-gal4. (J) Confocal image of a single brain hemisphere of MB018B for the MBON-α′2.DOI:http://dx.doi.org/10.7554/eLife.04580.028

Mentions: (A) Diagram of odor conditioning using ethanol vapor. Conditioned ethanol preference is measured by presenting two odors in sequence, one in the presence of an intoxicating dose of ethanol, three times for 10 min with 50-min breaks between exposures, followed by testing for preference between the two odors in a Y-maze in the absence of ethanol either 30 min or 24 hr after training. Wild-type flies find the ethanol-paired odor to be aversive when tested 30 min after training, but appetitive 24 hr after training. (B) Results of assays for the requirement of MBONs in ethanol-induced appetitive odor memory. pJFRC100-20XUAS-TTS-Shibire-ts1-p10 (VK00005) was used to block synaptic transmission during training and test; flies were kept at the permissive temperature for the 24 hr between training and test. MBONs have been grouped by neurotransmitter and color-coded. The bottom and top of each box represents the first and third quartile, and the horizontal line dividing the box is the median. The whiskers represent the 10th and 90th percentiles. The gray rectangle spanning the horizontal axis indicates the interquartile range of the control. Statistical tests are described in methods: *, p < 0.05; **, p < 0.01; ***, p < 0.001. The relative expression levels produced by the split-GAL4 driver lines in each cell type (indicated by the gray scale) are based on imaging with pJFRC2-10XUAS-IVS-mCD8::GFP (VK00005). Images of the expression patterns of selected drivers are shown in Figure 11—figure supplement 1. (C) 30-min ethanol-induced odor memory. (D) 24-hr ethanol-induced appetitive odor memory compared to +/Shi and GAL4/+ genetic controls. (E) Blocking transmission in MBON-α′2 with MB091C resulted in a failure to switch from aversive to appetitive memory for ethanol intoxication, confirming the result seen with MB018B. (F) Renderings of the MBONs implicated in 24 hr ethanol odor memory. MBONs grouped by square brackets represent cases where the available set of driver lines do not allow assigning an effect to a single cell type, but only to that set of MBONs. MBONs cell types in parentheses indicate cases where the data implicating them are only suggestive. (G) Schematic of potential circuits for appetitive ethanol memory. Cholinergic outputs from the MBON-α′2 and MBON-γ2α′1, and glutamatergic MBON-γ4>γ1γ2, MBON-γ5β′2a and MBON-β′2mp are implicated in appetitive ethanol memory. MBONs for which the data shows inconsistency across driver lines (MBON-α3 and MBON-γ2α′1) are shown in a lighter color; additional experiments will be required to resolve the role of these MBONs.


Mushroom body output neurons encode valence and guide memory-based action selection in Drosophila.

Aso Y, Sitaraman D, Ichinose T, Kaun KR, Vogt K, Belliart-Guérin G, Plaçais PY, Robie AA, Yamagata N, Schnaitmann C, Rowell WJ, Johnston RM, Ngo TT, Chen N, Korff W, Nitabach MN, Heberlein U, Preat T, Branson KM, Tanimoto H, Rubin GM - Elife (2014)

Expression patterns of split-GAL4s that caused odor-ethanol intoxication memory phenotypes.(A–I) Expression patterns of selected split-GAL4 drivers as assessed with pJFRC2-10XUAS-IVS-mCD8::GFP (VK00005). Full confocal stacks of these images are available at www.janelia.org/split-gal4. (J) Confocal image of a single brain hemisphere of MB018B for the MBON-α′2.DOI:http://dx.doi.org/10.7554/eLife.04580.028
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4273436&req=5

fig11s1: Expression patterns of split-GAL4s that caused odor-ethanol intoxication memory phenotypes.(A–I) Expression patterns of selected split-GAL4 drivers as assessed with pJFRC2-10XUAS-IVS-mCD8::GFP (VK00005). Full confocal stacks of these images are available at www.janelia.org/split-gal4. (J) Confocal image of a single brain hemisphere of MB018B for the MBON-α′2.DOI:http://dx.doi.org/10.7554/eLife.04580.028
Mentions: (A) Diagram of odor conditioning using ethanol vapor. Conditioned ethanol preference is measured by presenting two odors in sequence, one in the presence of an intoxicating dose of ethanol, three times for 10 min with 50-min breaks between exposures, followed by testing for preference between the two odors in a Y-maze in the absence of ethanol either 30 min or 24 hr after training. Wild-type flies find the ethanol-paired odor to be aversive when tested 30 min after training, but appetitive 24 hr after training. (B) Results of assays for the requirement of MBONs in ethanol-induced appetitive odor memory. pJFRC100-20XUAS-TTS-Shibire-ts1-p10 (VK00005) was used to block synaptic transmission during training and test; flies were kept at the permissive temperature for the 24 hr between training and test. MBONs have been grouped by neurotransmitter and color-coded. The bottom and top of each box represents the first and third quartile, and the horizontal line dividing the box is the median. The whiskers represent the 10th and 90th percentiles. The gray rectangle spanning the horizontal axis indicates the interquartile range of the control. Statistical tests are described in methods: *, p < 0.05; **, p < 0.01; ***, p < 0.001. The relative expression levels produced by the split-GAL4 driver lines in each cell type (indicated by the gray scale) are based on imaging with pJFRC2-10XUAS-IVS-mCD8::GFP (VK00005). Images of the expression patterns of selected drivers are shown in Figure 11—figure supplement 1. (C) 30-min ethanol-induced odor memory. (D) 24-hr ethanol-induced appetitive odor memory compared to +/Shi and GAL4/+ genetic controls. (E) Blocking transmission in MBON-α′2 with MB091C resulted in a failure to switch from aversive to appetitive memory for ethanol intoxication, confirming the result seen with MB018B. (F) Renderings of the MBONs implicated in 24 hr ethanol odor memory. MBONs grouped by square brackets represent cases where the available set of driver lines do not allow assigning an effect to a single cell type, but only to that set of MBONs. MBONs cell types in parentheses indicate cases where the data implicating them are only suggestive. (G) Schematic of potential circuits for appetitive ethanol memory. Cholinergic outputs from the MBON-α′2 and MBON-γ2α′1, and glutamatergic MBON-γ4>γ1γ2, MBON-γ5β′2a and MBON-β′2mp are implicated in appetitive ethanol memory. MBONs for which the data shows inconsistency across driver lines (MBON-α3 and MBON-γ2α′1) are shown in a lighter color; additional experiments will be required to resolve the role of these MBONs.

Bottom Line: The behavioral effects of MBON perturbation are combinatorial, suggesting that the MBON ensemble collectively represents valence.We propose that local, stimulus-specific dopaminergic modulation selectively alters the balance within the MBON network for those stimuli.Our results suggest that valence encoded by the MBON ensemble biases memory-based action selection.

View Article: PubMed Central - PubMed

Affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.

ABSTRACT
Animals discriminate stimuli, learn their predictive value and use this knowledge to modify their behavior. In Drosophila, the mushroom body (MB) plays a key role in these processes. Sensory stimuli are sparsely represented by ∼2000 Kenyon cells, which converge onto 34 output neurons (MBONs) of 21 types. We studied the role of MBONs in several associative learning tasks and in sleep regulation, revealing the extent to which information flow is segregated into distinct channels and suggesting possible roles for the multi-layered MBON network. We also show that optogenetic activation of MBONs can, depending on cell type, induce repulsion or attraction in flies. The behavioral effects of MBON perturbation are combinatorial, suggesting that the MBON ensemble collectively represents valence. We propose that local, stimulus-specific dopaminergic modulation selectively alters the balance within the MBON network for those stimuli. Our results suggest that valence encoded by the MBON ensemble biases memory-based action selection.

Show MeSH