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Autoregulatory and paracrine control of synaptic and behavioral plasticity by octopaminergic signaling

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Abstract

Adrenergic signaling has important roles in synaptic plasticity and metaplasticity. However, the underlying mechanisms of these functions remain poorly understood. We investigated the role of octopamine, the invertebrate counterpart of adrenaline and noradrenaline, in synaptic and behavioral plasticity in Drosophila. We found that an increase in locomotor speed induced by food deprivation was accompanied by an activity- and octopamine-dependent extension of octopaminergic arbors and that the formation and maintenance of these arbors required electrical activity. Growth of octopaminergic arbors was controlled by a cAMP- and CREB-dependent positive-feedback mechanism that required Octβ2R octopamine autoreceptors. Notably, this autoregulation was necessary for the locomotor response. In addition, octopamine neurons regulated the expansion of excitatory glutamatergic neuromuscular arbors through Octβ2Rs on glutamatergic motor neurons. Our results provide a mechanism for global regulation of excitatory synapses, presumably to maintain synaptic and behavioral plasticity in a dynamic range.

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Figure 1: Food-deprivation increase in larval locomotion is correlated with synaptopod formation at type II arbors.
Figure 2: Stepwise development of synaptopods.
Figure 3: Electrical activity and octopamine regulate the extension of synaptopods.
Figure 4: Innervation and maintenance of type II arbors depends on activity.
Figure 5: Synaptopod extension is regulated by the cAMP pathway and requires new protein synthesis and CREB.
Figure 6: Presynaptic Octβ2R autoreceptors, but not OAMB receptors, regulate the growth of type II arbors.
Figure 7: Type II motor neurons regulate the growth of type I arbors.

Change history

  • 16 January 2011

    In the version of this article initially published online, an error was made on page 2, left column, third paragraph, sixth line. The genotype 'tbhnM19' should read 'tbhnM18'. In the Online Methods, left column, first paragraph, fifth line, the genotype 'tbhnM189' should read 'tbhnM18 (ref. 9)'. Finally, in the Online Methods, right column, seventh paragraph, fourth line, the abbreviation 'Drc' should read 'Dcr'. These errors have been corrected for the print, PDF and HTML versions of this article.

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Acknowledgements

We thank M. Yoshihara, S. Speese, Y. Fuentes-Medel and C. Korkut for comments on the manuscript, C. Brewer for assistance with data analysis and the UMass Amherst antibody facility for production of the TBH antibody. This work was supported by US National Institutes of Health grants R01 MH0700000 to V.B., MH09883 to S.W., MH081982 to S.W. and GM084491 to M.J.A. M.J.A. was also supported by the Bill & Melinda Gates Foundation.

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Authors

Contributions

A.C.K. designed and performed most experiments and contributed to manuscript writing; J.A. contributed to tool development, electrophysiology, experimental design and manuscript writing; R.B. performed RT-PCR and some immunocytochemistry; S.W., S.D. and R.B. generated, characterized and validated PACα function; M.J.A. helped with the design of the TBH antibody; and V.B. directed the project and wrote the manuscript in collaboration with A.C.K. and J.A.

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Correspondence to Vivian Budnik.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–8 (PDF 894 kb)

Supplementary Movie 1

Dynamics of natural synaptopods at type-II arbors. (MOV 18 kb)

Supplementary Movie 2

Synaptopods develop ball-shaped varicosities. (MOV 252 kb)

Supplementary Movie 3

Secondary synaptopod formation on a varicosity. (MOV 109 kb)

Supplementary Movie 4

Induction of synaptopod formation upon acute increase in cAMP levels. (MOV 1384 kb)

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Koon, A., Ashley, J., Barria, R. et al. Autoregulatory and paracrine control of synaptic and behavioral plasticity by octopaminergic signaling. Nat Neurosci 14, 190–199 (2011). https://doi.org/10.1038/nn.2716

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