Perinatal Photoperiod Affects the Serotonergic System and Affective Behaviors

Abstract

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 and neurodevelopmental disorders, such as depression, anxiety and autism, and alterations in the serotonergic phenotype of raphe neurons has dramatic effects on affective behaviors in rodents. Here, I demonstrate that day length (photoperiod) during development induces enduring changes in mouse dorsal raphe serotonin neurons - programming their spontaneous neural activity, their responsiveness to noradrenergic stimulation, their intrinsic electrical properties, serotonin and norepinephrine content in the midbrain, gene expression of key serotonergic genes, the ratio of TPH2 positive cells to total cells in the dorsal raphe, as well as 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.