Article | Published:

Glia-derived neurons are required for sex-specific learning in C. elegans

Nature volume 526, pages 385390 (15 October 2015) | Download Citation

Abstract

Sex differences in behaviour extend to cognitive-like processes such as learning, but the underlying dimorphisms in neural circuit development and organization that generate these behavioural differences are largely unknown. Here we define at the single-cell level—from development, through neural circuit connectivity, to function—the neural basis of a sex-specific learning in the nematode Caenorhabditis elegans. We show that sexual conditioning, a form of associative learning, requires a pair of male-specific interneurons whose progenitors are fully differentiated glia. These neurons are generated during sexual maturation and incorporated into pre-exisiting sex-shared circuits to couple chemotactic responses to reproductive priorities. Our findings reveal a general role for glia as neural progenitors across metazoan taxa and demonstrate that the addition of sex-specific neuron types to brain circuits during sexual maturation is an important mechanism for the generation of sexually dimorphic plasticity in learning.

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Acknowledgements

We would like to acknowledge M. Barr, in whose laboratory A.B. discovered the MCMs; WormAtlas for illustrations (reproduced with permission); T. Jarrell for contributions to the EM reconstruction; and W. Letton for the generation of strains and preliminary ablation studies. We thank M. Boxem, D. Portman, H. Baylis, L. Bianchi and R. Garcia for strains and reagents; M. Zhen, O. Hobert, I. Carrera, N. Stefanakis and S. Shaham, for unpublished reagents. Purified ascarosides were a gift from F. Schroeder to the Barr laboratory. Additional strains were obtained from the CGC, which is funded by NIH grant P40 OD010440. We thank L. Cochella, I. Carrera, S. Jarriault, and several of our close colleagues in CDB and NPP at University College London for discussions and comments on the manuscript; C. Barnes for advice on statistical analysis. This work was supported by a Master it! Scholarship Scheme (Malta and EU) to M.S., by NIH grant OD010943 to D.H.H., by Marie Curie CIG grant 618779 to R.J.P. and by a grant from The G. Harold and Leila Y. Mathers Charitable Foundation to S.W.E.; S.J.C. is supported by NIH grant 5T32GM007491; R.J.P. is a Wellcome Trust Research Career Development Fellow 095722/Z/11/Z; A.B. is supported by the Wellcome Trust Institutional Strategic Support Fund 097815/Z/11/A.

Author information

Author notes

    • Richard J. Poole
    •  & Arantza Barrios

    These authors contributed equally to this work.

Affiliations

  1. Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK

    • Michele Sammut
    • , Terry Felton
    • , Richard J. Poole
    •  & Arantza Barrios
  2. Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA

    • Steven J. Cook
    • , Ken C. Q. Nguyen
    • , David H. Hall
    •  & Scott W. Emmons
  3. Department of Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA

    • Scott W. Emmons

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Contributions

M.S., T.F., R.J.P. and A.B. conceived and performed the development and behaviour experiments. S.J.C., K.C.Q.N., S.W.E. and D.H.H. performed the ultrastructural analysis of the MCMs. S.J.C. and S.W.E. reconstructed the connectivity of the MCMs from serial EM sections. R.J.P. and A.B. co-wrote the manuscript and discussed it with all the authors.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Richard J. Poole or Arantza Barrios.

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https://doi.org/10.1038/nature15700

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