Photoperiodic Programming of Serotonin Neurons

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PROJECT SUMMARY A fundamental question in neuroscience is how environmental signals may have long-lasting effects on neural circuits and neural function. The circadian clock and circadian photoperiod are associated with mood disorders, but the neurobiological mechanisms are unknown. Dysregulation of serotonin neurotransmission is implicated in neurobehavioral disorders, such as depression and anxiety, and alterations in the serotonergic phenotype of raphe neurons has dramatic effects on affective behaviors in rodents. The serotonergic dorsal raphe nuclei receive light input from the circadian visual system, as well as polysynaptic input from the biological clock nuclei, and dorsal raphe serotonin neurons respond acutely to tonic illumination with increased spike rate and to changes in the circadian light cycle with gene activation. Our laboratory has demonstrated that seasonal circadian photoperiods (winter –like “short days” vs. summer-like “long days”) can induce enduring changes in mouse dorsal raphe serotonin neurons - programming their spontaneous neural activity, and altering depression and anxiety-like behaviors. Here we seek to elucidate the mechanistic basis photoperiodic programming of serotonin neurons, focusing on electrophysiology, gene regulation and maternal-fetal vs neonatal developmental windows. We will examine neural mechanisms of photoperiodic programming of dorsal raphe serotonin neurons using both multi-electrode array and whole cell electrophysiology; altered gene regulation in serotonin neurons induced by photoperiodic programming using RT-PCR, RNA-seq gene expression analysis of FACS sorted serotonin neurons and RNA Scope in situ hybridization to determine the photoperiod programming transcriptome, and the gene network in serotonergic neurons driven by photoperiodic programming. We will test the hypothesis that the Pet-1 transcription factor is a critical node for photoperiodic programing and define critical periods for the enduring effects of photoperiod. Successful completion of these aims will reveal novel mechanisms by which a pervasive environmental signal – the daily light cycle – can influence the long-term function of brain serotonergic neurons and the behaviors they mediate.