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Lasting synaptic changes underlie attention deficits caused by nicotine exposure during adolescence

Nature Neuroscience volume 14, pages 417–419 (2011)Cite this article

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Abstract

Tobacco smoking and nicotine exposure during adolescence interfere with prefrontal cortex (PFC) development and lead to cognitive impairments in later life. The molecular and cellular underpinnings of these consequences remain elusive. We found that adolescent nicotine exposure induced lasting attentional disturbances and reduced mGluR2 protein and function on presynaptic terminals of PFC glutamatergic synapses. Restoring mGluR2 activity in vivo by local infusion of a group II mGluR agonist in adult rats that received nicotine as adolescents rescued attentional disturbances.

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Figure 1: Adolescent nicotine exposure affects measures of attentional performance, mGluR2 levels and long-term function on the long term.
Figure 2: Short-term depression in mPFC is reduced 5 weeks after nicotine exposure during adolescence.
Figure 3: Intra-mPFC infusion of mGluR2/3 agonist LY379268 reverses long-term attentional disturbances in rats exposed to nicotine as adolescents.

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Acknowledgements

We thank Y. van Mourik, M. Stegeman, H. Lodder, B. Lodder, C. de Kock and R. Binnekade for excellent technical assistance. Funding was received from Netherlands Organization for Scientific Research (D.S.C., N.A.G., S.S., H.D.M., T.P., A.N.M.S. and A.B.S.), Center for Medical Systems Biology (K.W.L. and R.C.v.d.S.) and VU University (H.D.M.; Starting Independent Research Grant, VU European Research Council).

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Author notes

  1. Huibert D Mansvelder, Tommy Pattij and Sabine Spijker: These authors contributed equally to this work.

Authors and Affiliations

  1. Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, The Netherlands

    Danielle S Counotte, Ka Wan Li, Maarten Loos, Roel C van der Schors, August B Smit & Sabine Spijker

  2. Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, The Netherlands

    Natalia A Goriounova & Huibert D Mansvelder

  3. Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands

    Dustin Schetters, Anton N M Schoffelmeer & Tommy Pattij

Authors
  1. Danielle S Counotte
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Contributions

D.S.C. and N.A.G. contributed equally to the experiments in this paper. D.S.C., K.W.L., A.B.S. and S.S. designed the molecular experiments. N.A.G. and H.D.M. designed the physiological experiments. D.S.C., A.N.M.S., S.S. and T.P. designed the behavioral experiments. D.S.C. and R.C.v.d.S. executed the molecular experiments. N.A.G. executed physiological experiments. D.S.C. and D.S. executed behavioral experiments. D.S.C., M.L. and S.S. analyzed molecular experiments. N.A.G. and H.D.M. analyzed physiological experiments. D.S.C. and T.P. analyzed behavioral experiments. D.S.C., H.D.M., T.P. and S.S. wrote the manuscript.

Corresponding author

Correspondence to Sabine Spijker.

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The authors declare no competing financial interests.

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Supplementary Figures 1–10, Supplementary Tables 1–4, Supplementary Methods, Supplementary Results and Supplementary Discussion (PDF 2357 kb)

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Counotte, D., Goriounova, N., Li, K. et al. Lasting synaptic changes underlie attention deficits caused by nicotine exposure during adolescence. Nat Neurosci 14, 417–419 (2011). https://doi.org/10.1038/nn.2770

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