Illumination controls differentiation of dopamine neurons regulating behaviour

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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.


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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) doi:10.1038/nature07569

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