Photoperiod programs dorsal raphe serotonergic neurons and affective behaviors

Curr Biol. 2015 May 18;25(10):1389-94. doi: 10.1016/j.cub.2015.03.050. Epub 2015 May 7.


The serotonergic raphe nuclei of the midbrain are principal centers from which serotonin neurons project to innervate cortical and sub-cortical structures. The dorsal raphe nuclei receive light input from the circadian visual system and indirect input from the biological clock nuclei. Dysregulation of serotonin neurotransmission is implicated in neurobehavioral disorders, such as depression and anxiety, and alterations in the serotonergic phenotype of raphe neurons have dramatic effects on affective behaviors in rodents. Here, we demonstrate that day length (photoperiod) during development induces enduring changes in mouse dorsal raphe serotonin neurons—programming their firing rate, responsiveness to noradrenergic stimulation, intrinsic electrical properties, serotonin and norepinephrine content in the midbrain, and depression/anxiety-related behavior in a melatonin receptor 1 (MT1)-dependent manner. Our results establish mechanisms by which seasonal photoperiods may dramatically and persistently alter the function of serotonin neurons.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Adrenergic alpha-1 Receptor Agonists / pharmacology
  • Animals
  • Dorsal Raphe Nucleus / drug effects
  • Dorsal Raphe Nucleus / physiology*
  • Dose-Response Relationship, Drug
  • Female
  • Male
  • Mesencephalon / physiology
  • Mice, Inbred C3H
  • Mice, Knockout
  • Norepinephrine / physiology
  • Organ Culture Techniques
  • Phenylephrine / pharmacology
  • Photoperiod*
  • Receptor, Melatonin, MT1 / genetics
  • Receptor, Melatonin, MT1 / metabolism
  • Serotonergic Neurons / drug effects
  • Serotonergic Neurons / physiology*
  • Serotonin / physiology
  • Serotonin Receptor Agonists / pharmacology


  • Adrenergic alpha-1 Receptor Agonists
  • Receptor, Melatonin, MT1
  • Serotonin Receptor Agonists
  • Phenylephrine
  • Serotonin
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Norepinephrine