Limits...
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.

Show MeSH
Expression patterns of split-GAL4s that caused sleep phenotypes.(A–L) Expression patterns of selected split-GAL4 lines are shown, as assessed with pJFRC200-10XUAS-IVS-myr::smGFP-HA (attP18). Full confocal stacks of these images are available at www.janelia.org/split-gal4.DOI:http://dx.doi.org/10.7554/eLife.04580.030
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4273436&req=5

fig12s1: Expression patterns of split-GAL4s that caused sleep phenotypes.(A–L) Expression patterns of selected split-GAL4 lines are shown, as assessed with pJFRC200-10XUAS-IVS-myr::smGFP-HA (attP18). Full confocal stacks of these images are available at www.janelia.org/split-gal4.DOI:http://dx.doi.org/10.7554/eLife.04580.030

Mentions: (A) Top: Schematic of the experimental apparatus used for assaying sleep. Single flies are placed in a tube and activity is measured by counting the number of times the fly crosses an infrared beam. Bottom: Diagram of the experimental assay. Sleep was measured at 21.5°C for 3 days to establish the baseline sleep profile. Flies were then shifted to 28.5°C for 2 days to increase activity of the targeted cells by activating the dTrpA1 channel, and then returned to 21.5°C after activation to assay recovery. The effect of MBON activation on sleep amount is quantified as percentage change in sleep. Negative and positive values indicate decreased and increased sleep, respectively. (B) Box plots of change in sleep induced by dTrpA1 [UAS-dTrpA1 (attP16); (Hamada et al., 2008)] mediated activation of the neurons targeted by each of the indicated split-GAL4 driver lines. MBONs are grouped by neurotransmitter and color-coded as indicated. 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 matrix below the box plots shows the relative levels of expression (indicated by the gray scale) in the cell types observed with each driver line using pJFRC200-10XUAS-IVS-myr::smGFP-HA (attP18). Images of the expression patterns of selected drivers are shown in Figure 12—figure supplement 1. (C) Sleep profiles of four split-GAL4 lines are shown. Each plot shows a 4-day period starting with subjective dawn. Sleep duration (min/30 min) on day 3 (21.5°C; permissive temperature), days 4, 5 (28.5°C; non-permissive temperature) and day 6 (21.5°C; permissive temperature) are plotted (colored line, split-GAL4 line in combination with pJFRC124-20XUAS-IVS-dTrpA1 (attP18); black line, represents +/dTrpA1; gray line, split-GAL4/+). (D) Sleep phenotypes were replicated with pJFRC124-20XUAS-IVS-dTrpA1 (attP18) for the eight drivers shown, but not for MB242A (not shown). Corresponding split-GAL4/+ flies showed normal sleep. (E, F) Renderings of MBONs responsible for the decreasing (E) or increasing (F) sleep. MBONs are color-coded based on their putative transmitter. (G) Diagram of MBONs responsible for the sleep regulation. MBONs are color-coded based on their putative transmitter as indicated. The wake promoting glutamatergic MBON-γ5β′2a, MBON-β′2mp and MBON-β′2mp_bilateral converge with the sleep promoting cholinergic MBON-γ2α′1 and GABAergic MBON-γ3 and MBON-γ3β′1 in the SMP and CRE. The wake-promoting glutamatergic MBON-γ4>γ1γ2 terminates in the dendritic region of MBON-γ2α′1.


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 sleep phenotypes.(A–L) Expression patterns of selected split-GAL4 lines are shown, as assessed with pJFRC200-10XUAS-IVS-myr::smGFP-HA (attP18). Full confocal stacks of these images are available at www.janelia.org/split-gal4.DOI:http://dx.doi.org/10.7554/eLife.04580.030
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4273436&req=5

fig12s1: Expression patterns of split-GAL4s that caused sleep phenotypes.(A–L) Expression patterns of selected split-GAL4 lines are shown, as assessed with pJFRC200-10XUAS-IVS-myr::smGFP-HA (attP18). Full confocal stacks of these images are available at www.janelia.org/split-gal4.DOI:http://dx.doi.org/10.7554/eLife.04580.030
Mentions: (A) Top: Schematic of the experimental apparatus used for assaying sleep. Single flies are placed in a tube and activity is measured by counting the number of times the fly crosses an infrared beam. Bottom: Diagram of the experimental assay. Sleep was measured at 21.5°C for 3 days to establish the baseline sleep profile. Flies were then shifted to 28.5°C for 2 days to increase activity of the targeted cells by activating the dTrpA1 channel, and then returned to 21.5°C after activation to assay recovery. The effect of MBON activation on sleep amount is quantified as percentage change in sleep. Negative and positive values indicate decreased and increased sleep, respectively. (B) Box plots of change in sleep induced by dTrpA1 [UAS-dTrpA1 (attP16); (Hamada et al., 2008)] mediated activation of the neurons targeted by each of the indicated split-GAL4 driver lines. MBONs are grouped by neurotransmitter and color-coded as indicated. 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 matrix below the box plots shows the relative levels of expression (indicated by the gray scale) in the cell types observed with each driver line using pJFRC200-10XUAS-IVS-myr::smGFP-HA (attP18). Images of the expression patterns of selected drivers are shown in Figure 12—figure supplement 1. (C) Sleep profiles of four split-GAL4 lines are shown. Each plot shows a 4-day period starting with subjective dawn. Sleep duration (min/30 min) on day 3 (21.5°C; permissive temperature), days 4, 5 (28.5°C; non-permissive temperature) and day 6 (21.5°C; permissive temperature) are plotted (colored line, split-GAL4 line in combination with pJFRC124-20XUAS-IVS-dTrpA1 (attP18); black line, represents +/dTrpA1; gray line, split-GAL4/+). (D) Sleep phenotypes were replicated with pJFRC124-20XUAS-IVS-dTrpA1 (attP18) for the eight drivers shown, but not for MB242A (not shown). Corresponding split-GAL4/+ flies showed normal sleep. (E, F) Renderings of MBONs responsible for the decreasing (E) or increasing (F) sleep. MBONs are color-coded based on their putative transmitter. (G) Diagram of MBONs responsible for the sleep regulation. MBONs are color-coded based on their putative transmitter as indicated. The wake promoting glutamatergic MBON-γ5β′2a, MBON-β′2mp and MBON-β′2mp_bilateral converge with the sleep promoting cholinergic MBON-γ2α′1 and GABAergic MBON-γ3 and MBON-γ3β′1 in the SMP and CRE. The wake-promoting glutamatergic MBON-γ4>γ1γ2 terminates in the dendritic region of MBON-γ2α′1.

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