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Illumination controls differentiation of dopamine neurons regulating behaviour

Abstract

Specification of the appropriate neurotransmitter is a crucial step in neuronal differentiation because it enables signalling among populations of neurons. Experimental manipulations demonstrate that both autonomous and activity-dependent genetic programs contribute to this process during development, but whether natural environmental stimuli specify transmitter expression in a neuronal population is unknown. We investigated neurons of the ventral suprachiasmatic nucleus that regulate neuroendocrine pituitary function in response to light in teleosts, amphibia and primates. Here we show that altering light exposure, which changes the sensory input to the circuit controlling adaptation of skin pigmentation to background, changes the number of neurons expressing dopamine in larvae of the amphibian Xenopus laevis in a circuit-specific and activity-dependent manner. Neurons newly expressing dopamine then regulate changes in camouflage colouration in response to illumination. Thus, physiological activity alters the numbers of behaviourally relevant amine-transmitter-expressing neurons in the brain at postembryonic stages of development. The results may be pertinent to changes in cognitive states that are regulated by biogenic amines.

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Figure 1: Dopaminergic VSC neurons regulate skin pigmentation.
Figure 2: Dopaminergic differentiation is activity-dependent.
Figure 3: Illumination changes the number of dopaminergic neurons selectively in the VSC.
Figure 4: Blocking physiological activity eliminates illumination-dependent changes in the number of dopaminergic VSC neurons.
Figure 5: NPY neurons projecting to melanotrope cells express TH after illumination.
Figure 6: Newly dopaminergic neurons regulate pigmentation.

References

  1. Walicke, P. A. & Patterson, P. H. On the role of Ca2+ in the transmitter choice made by cultured sympathetic neurons. J. Neurosci. 1, 343–350 (1981)

    Article  CAS  Google Scholar 

  2. Brosenitsch, T. A. & Katz, D. M. Expression of Phox2 transcription factors and induction of the dopaminergic phenotype in primary sensory neurons. Mol. Cell. Neurosci. 20, 447–457 (2002)

    Article  CAS  Google Scholar 

  3. Borodinsky, L. N. et al. Activity-dependent homeostatic specification of transmitter expression in embryonic neurons. Nature 429, 523–530 (2004)

    Article  ADS  CAS  Google Scholar 

  4. Gomez-Lira, G., Lamas, M., Romo-Parra, H. & Gutierrez, R. Programmed and induced phenotype of the hippocampal granule cells. J. Neurosci. 25, 6939–6946 (2005)

    Article  CAS  Google Scholar 

  5. Catalano, S. M., Chang, C. K. & Shatz, C. J. Activity-dependent regulation of NMDAR1 immunoreactivity in the developing visual cortex. J. Neurosci. 17, 8376–8390 (1997)

    Article  CAS  Google Scholar 

  6. Kidd, F. L. & Isaac, J. T. R. Developmental and activity-dependent regulation of kainate receptors at thalamocortical synapses. Nature 400, 569–573 (1999)

    Article  ADS  CAS  Google Scholar 

  7. Shi, J., Townsend, M. & Constantine-Paton, M. Activity-dependent induction of tonic calcineurin activity mediates a rapid developmental downregulation of NMDA receptor currents. Neuron 28, 103–114 (2000)

    Article  CAS  Google Scholar 

  8. Brunelli, G. et al. Glutamatergic reinnervation through peripheral nerve graft dictates assembly of glutamatergic synapses at rat skeletal muscle. Proc. Natl Acad. Sci. USA 102, 8752–8757 (2005)

    Article  ADS  CAS  Google Scholar 

  9. Borodinsky, L. N. & Spitzer, N. C. Activity-dependent neurotransmitter-receptor matching at the neuromuscular junction. Proc. Natl Acad. Sci. USA 104, 335–340 (2007)

    Article  ADS  CAS  Google Scholar 

  10. Fletcher, C. F. et al. Absence epilepsy in tottering mutant mice is associated with calcium channel defects. Cell 87, 607–617 (1996)

    Article  CAS  Google Scholar 

  11. Hess, E. J. & Wilson, M. C. Tottering and leaner mutations perturb transient developmental expression of tyrosine-hydroxylase in embryologically distinct Purkinje-cells. Neuron 6, 123–132 (1991)

    Article  CAS  Google Scholar 

  12. Ubink, R., Tuinhof, R. & Roubos, E. W. Identification of suprachiasmatic melanotrope-inhibiting neurons in Xenopus laevis: A confocal laser-scanning microscopy study. J. Comp. Neurol. 397, 60–68 (1998)

    Article  CAS  Google Scholar 

  13. Tuinhof, R. et al. Involvement of retinohypothalamic input, suprachiasmatic nucleus, magnocellular nucleus and locus-coeruleus in control of melanotrope cells of Xenopus-laevis — a retrograde and anterograde tracing study. Neuroscience 61, 411–420 (1994)

    Article  CAS  Google Scholar 

  14. Kramer, B. M. R. et al. Dynamics and plasticity of peptidergic control centres in the retino–brain–pituitary system of Xenopus laevis . Microsc. Res. Tech. 54, 188–199 (2001)

    Article  ADS  CAS  Google Scholar 

  15. Kolk, S. M., Berghs, C., Vaudry, H., Verhage, M. & Roubos, E. W. Physiological control of Xunc18 expression in neuroendocrine melanotrope cells of Xenopus laevis . Endocrinology 142, 1950–1957 (2001)

    Article  CAS  Google Scholar 

  16. Abizaid, A., Horvath, B., Keefe, D. L., Leranth, C. & Horvath, T. L. Direct visual and circadian pathways target neuroendocrine cells in primates. Eur. J. Neurosci. 20, 2767–2776 (2004)

    Article  Google Scholar 

  17. Logan, D. W., Burn, S. F. & Jackson, I. J. Regulation of pigmentation in zebrafish melanophores. Pigment Cell Res. 19, 206–213 (2006)

    Article  CAS  Google Scholar 

  18. Roubos, E. W., Scheenen, W. & Jenks, B. G. in Trends in Comparative Endocrinology and Neurobiology 172–183. (2005)

    Google Scholar 

  19. Nordland, J. J. et al. The Pigmentary System: Physiology and Pathophysiology (Oxford Univ. Press, 2006)

    Book  Google Scholar 

  20. Tonosaki, Y., Nishiyama, K., Honda, T., Ozaki, N. & Sugiura, Y. D-2-like dopamine-receptor mediates dopaminergic or gamma-aminobutyric acidergic inhibition of melanotropin-releasing hormone release from the pars intermedia in frogs (Rana-nigromaculata). Endocrinology 136, 5260–5265 (1995)

    Article  CAS  Google Scholar 

  21. Akopian, A. & Witkovsky, P. D2 dopamine receptor-mediated inhibition of a hyperpolarization-activated current in rod photoreceptors. J. Neurophysiol. 76, 1828–1835 (1996)

    Article  CAS  Google Scholar 

  22. Wang, Y., Harsanyi, K. & Mangel, S. C. Endogenous activation of dopamine D2 receptors regulates dopamine release in the fish retina. J. Neurophysiol. 78, 439–449 (1997)

    Article  CAS  Google Scholar 

  23. Li, L. & Dowling, J. E. Effects of dopamine depletion on visual sensitivity of zebrafish. J. Neurosci. 20, 1893–1903 (2000)

    Article  CAS  Google Scholar 

  24. Green, C. B., Liang, M. Y., Steenhard, B. M. & Besharse, J. C. Ontogeny of circadian and light regulation of melatonin release in Xenopus laevis embryos. Dev. Brain Res. 117, 109–116 (1999)

    Article  CAS  Google Scholar 

  25. Mastick, G. S. & Andrews, G. L. Pax6 regulates the identity of embryonic diencephalic neurons. Mol. Cell. Neurosci. 17, 190–207 (2001)

    Article  CAS  Google Scholar 

  26. Wullimann, M. F. & Rink, E. Detailed immunohistology of Pax6 protein and tyrosine hydroxylase in the early zebrafish brain suggests role of Pax6 gene in development of dopaminergic diencephalic neurons. Dev. Brain Res. 131, 173–191 (2001)

    Article  CAS  Google Scholar 

  27. Vazquez-Martinez, R. et al. Melanotrope cell plasticity: a key mechanism for the physiological adaptation to background color changes. Endocrinology 142, 3060–3067 (2001)

    Article  CAS  Google Scholar 

  28. Berghs, C., Tanaka, S., VanStrien, F. J. C., Kurabuchi, S. & Roubos, E. W. The secretory granule and pro-opiomelanocortin processing in Xenopus melanotrope cells during background adaptation. J. Histochem. Cytochem. 45, 1673–1682 (1997)

    Article  CAS  Google Scholar 

  29. Zhang, H. et al. Calcium channel kinetics of melanotrope cells in Xenopus laevis depend on environmental stimulation. Gen. Comp. Endocrinol. 156, 104–112 (2008)

    Article  CAS  Google Scholar 

  30. Jenks, B. G., Kidane, A. H., Scheenen, W. & Roubos, E. W. Plasticity in the melanotrope neuroendocrine interface of Xenopus laevis . Neuroendocrinology 85, 177–185 (2007)

    Article  CAS  Google Scholar 

  31. Lam, C. S., Korzh, V. & Strahle, U. Zebrafish embryos are susceptible to the dopaminergic neurotoxin MPTP. Eur. J. Neurosci. 21, 1758–1762 (2005)

    Article  Google Scholar 

  32. McKinley, E. T. et al. Neuroprotection of MPTP-induced toxicity in zebrafish dopaminergic neurons. Brain Res. Mol. Brain Res. 141, 128–137 (2005)

    Article  CAS  Google Scholar 

  33. Olive, S., Rougon, G., Pierre, K. & Theodosis, D. T. Expression of a glycosyl phosphatidylinositol-anchored adhesion molecule, the glycoprotein F3, in the adult rat hypothalamoneurohypophyseal system. Brain Res. 689, 271–280 (1995)

    Article  CAS  Google Scholar 

  34. El Majdoubi, M., Poulain, D. A. & Theodosis, D. T. Activity-dependent morphological synaptic plasticity in an adult neurosecretory system: magnocellular oxytocin neurons of the hypothalamus. Biochem. Cell Biol. 78, 317–327 (2000)

    Article  CAS  Google Scholar 

  35. Mueller, N. K., Di, S., Paden, C. M. & Herman, J. P. Activity-dependent modulation of neurotransmitter innervation to vasopressin neurons of the supraoptic nucleus. Endocrinology 146, 348–354 (2005)

    Article  CAS  Google Scholar 

  36. Froemke, R. C., Merzenich, M. M. & Schreiner, C. E. A synaptic memory trace for cortical receptive field plasticity. Nature 450, 425–429 (2007)

    Article  ADS  CAS  Google Scholar 

  37. Lam, R. W. & Levitan, R. D. Pathophysiology of seasonal affective disorder: a review. J. Psychiatry Neurosci. 25, 469–480 (2000)

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Lam, R. W. & Levitt, A. J. Canadian Consensus Guidelines for the Treatment of Seasonal Affective Disorder (Clinical and Academic Publishing, 1999)

    Google Scholar 

  39. Lam, R. W., Tam, E. M., Grewal, A. & Yatham, L. N. Effects of α-methyl-para-tyrosine-induced catecholamine depletion in patients with seasonal affective disorder in summer remission. Neuropsychopharmacology 25, S97–S101 (2001)

    Article  CAS  Google Scholar 

  40. Michel, S., Itri, J. & Colwell, C. S. Excitatory mechanisms in the suprachiasmatic nucleus: the role of AMPA/KA glutamate receptors. J. Neurophysiol. 88, 817–828 (2002)

    Article  CAS  Google Scholar 

  41. Baquet, Z. C., Bickford, P. C. & Jones, K. R. Brain-derived neurotrophic factor is required for the establishment of the proper number of dopaminergic neurons in the substantia nigra pars compActa. J. Neurosci. 25, 6251–6259 (2005)

    Article  CAS  Google Scholar 

  42. McFarlane, S., McNeill, L. & Holt, C. E. FGF signaling and target recognition in the developing Xenopus visual system. Neuron 15, 1017–1028 (1995)

    Article  CAS  Google Scholar 

  43. Kim, J. et al. A microRNA feedback circuit in midbrain dopamine neurons. Science 317, 1220–1224 (2007)

    Article  ADS  CAS  Google Scholar 

  44. Goridis, C. & Rohrer, H. Specification of catecholaminergic and serotonergic neurons. Nature Rev. Neurosci. 3, 531–541 (2002)

    Article  CAS  Google Scholar 

  45. Obernosterer, G., Martinez, J. & Alenius, M. Locked nucleic acid-based in situ detection of microRNAs in mouse tissue sections. Nature Protocols 2, 1508–1514 (2007)

    Article  CAS  Google Scholar 

  46. Gonzalez, A. & Smeets, W. Comparative analysis of dopamine and tyrosine hydroxylase immunoreactivities in the brain of 2 amphibians, the anuran Rana ridibunda and the urodele Pleurodeles waltlii . J. Comp. Neurol. 303, 457–477 (1991)

    Article  CAS  Google Scholar 

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Acknowledgements

We thank D. Berg, L. Borodinsky and R. Levine for critical comments on the manuscript and I-T. Hsieh and D. Boassa for technical support. This work was supported by a grant to N.C.S. from the National Institutes of Health.

Author Contributions D.D. and N.C.S. planned the project, D.D. designed and carried out the experiments and performed data analysis, and D.D. and N.C.S. wrote the manuscript.

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Correspondence to Davide Dulcis.

Supplementary information

Supplementary Information 1

This file contains Supplementary Figures 1-4, 6-12 and 14-17 with Legends. (PDF 10680 kb)

Supplementary Video 1

Supplementary Figure 5 is a video file illustrating calcium transients in the hypothalamus of the stage 35 control larva illustrated in Supplementary Figure 4. The video was generated by acquiring a Fluo-4 confocal image series (1 frame/5 sec) for 15 min and digitally resampling it to play 60 times faster. Calcium spikes occur with a15% incidence at this stage. (AVI 25855 kb)

Supplementary Video 2

Supplementary Figure 13 Following adaptation in the light for 2 hr, annular neurons, identified by NPY expression (red), co-express TH (green) in their somata and axonal projections (yellow) to the melanotrope cells. 3-D video of VSC reconstruction obtained by merging confocal stacks imaged through a brain wholemount from a white-adapted stage 42 larva. Scale bar: 50 µm. (AVI 35762 kb)

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Dulcis, D., Spitzer, N. Illumination controls differentiation of dopamine neurons regulating behaviour. Nature 456, 195–201 (2008). https://doi.org/10.1038/nature07569

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