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Slow oscillations in two pairs of dopaminergic neurons gate long-term memory formation in Drosophila

Abstract

A fundamental duty of any efficient memory system is to prevent long-lasting storage of poorly relevant information. However, little is known about dedicated mechanisms that appropriately trigger production of long-term memory (LTM). We examined the role of Drosophila dopaminergic neurons in the control of LTM formation and found that they act as a switch between two exclusive consolidation pathways leading to LTM or anesthesia-resistant memory (ARM). Blockade, after aversive olfactory conditioning, of three pairs of dopaminergic neurons projecting on mushroom bodies, the olfactory memory center, enhanced ARM, whereas their overactivation conversely impaired ARM. Notably, blockade of these neurons during the intertrial intervals of a spaced training precluded LTM formation. Two pairs of these dopaminergic neurons displayed sustained calcium oscillations in naive flies. Oscillations were weakened by ARM-inducing massed training and were enhanced during LTM formation. Our results indicate that oscillations of two pairs of dopaminergic neurons control ARM levels and gate LTM.

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Figure 1: Th-GAL4 neurons regulate ARM consolidation.
Figure 2: Three pairs of dopaminergic neurons recapitulate the ARM-regulating properties of Th-GAL4 neurons.
Figure 3: Spontaneous sustained activity in MV1 and MP1 neurons of naive flies.
Figure 4: Oscillations in MV1 and MP1 neurons are correlated with ARM regulation.
Figure 5: ARM is absent after spaced conditioning.
Figure 6: Spaced training consistently promotes oscillatory behavior in MV1 and MP1 neurons.
Figure 7: ARM-inhibiting neurons gate long-term memory formation.

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Acknowledgements

We thank A. Pascual (Instituto de Biomedicina de Sevilla) and members of the Genes and Dynamics of Memory Systems group for critical reading of the manuscript. This work was supported by grants from the Agence Nationale pour la Recherche (T.P.), the Fondation pour la Recherche Médicale (T.P.), the Fondation Bettencourt-Schueller (T.P.), the Emmy-Noether Program from Deutsche Forschungsgemeinschaft (H.T.), the Bernstein focus Learning from Bundesministerium für Bildung und Forschung (H.T.) and the Max-Planck-Gesellschaft (H.T.). P.-Y.P. was supported by a grant from Région Ile-de-France, G.I. and S.T. by the Fondation pour la Recherche Médicale, and Y.A. by Deutscher Akademischer Austausch Dienst.

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Authors

Contributions

S.B., G.I. and T.P. were involved in the original design of the study. Behavioral experiments were performed by G.I. (Figs. 1, 5a and 7a, and Supplementary Fig. 1), S.T. (Figs. 2, 5c,d and 7b,d,e, and Supplementary Figs. 2 and 7), P.-Y.P. (Fig. 5b and Supplementary Fig. 5a) and G.B.-G. (Supplementary Fig. 6c). P.-Y.P. carried out all of the calcium imaging experiments and data analyses, except for the rsh experiment that was perfomed by G.B.-G. (Supplementary Fig. 6a,b). Y.A., I.S. and H.T. performed immunohistochemistry and analyzed the results. S.B. provided some fly stocks. P.V. provided financial support. P.-Y.P. and T.P. wrote the manuscript. T.P. designed the study and supervised the work. All of the authors discussed the results and commented on the manuscript.

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Correspondence to Thomas Preat.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–8 (PDF 2867 kb)

Supplementary Movie 1

Confocal stack showing the NP47-GAL4 expression pattern visualized by mCD8::GFP (white). Neuropils are counterlabeled with an anti-synapsin antibody (orange). (AVI 3264 kb)

Supplementary Movie 2

Confocal stack showing the NP47-GAL4 expression pattern visualized by mCD8::GFP (white). TH immunoreactive cells are labeled in magenta. (AVI 2811 kb)

Supplementary Movie 3

Confocal stack showing the NP47-GAL4 expression pattern, in combination with TH-GAL80, visualized by mCD8::GFP (white). Neuropils are counterlabeled with an anti-synapsin antibody (orange). (AVI 2962 kb)

Supplementary Movie 4

Confocal stack showing the NP47-GAL4 expression pattern, in combination with TH-GAL80, visualized by mCD8::GFP (white). TH immunoreactive cells are labeled in magenta. (AVI 2600 kb)

Supplementary Movie 5

Spontaneous activity oscillations in MB projections from MV1/MP1 neurons. This movie is accelerated 10 times; the real duration of the recording was 330 s. Oscillation characteristics were: left hemisphere: f0 = 0.11 Hz, Q = 2.1, amplitude 29% and right hemisphere: f0 = 0.105 Hz, Q = 1.6 amplitude 32%. Raw 8-bit grayscale images were smoothed with a 2-pixel radius Gaussian filter, a constant value of 30 was substracted from the resulting whole images, and contrast was then enhanced by rescaling intensity to reach 1.5% saturated pixels on one oscillation peak image (image processing performed with ImageJ). (AVI 3391 kb)

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Plaçais, PY., Trannoy, S., Isabel, G. et al. Slow oscillations in two pairs of dopaminergic neurons gate long-term memory formation in Drosophila. Nat Neurosci 15, 592–599 (2012). https://doi.org/10.1038/nn.3055

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