Sex differences in serotonergic control of daytime activities in diurnal Nile grass rats

Abstract

The mechanisms underlying day-active behaviors in diurnal species are still unclear. We lesioned midbrain serotonergic neurons and monitored the effect on spontaneous locomotor activity in diurnal Nile grass rats. First, serotonergic neuron localization was visualized by tryptophan hydroxylase 2 immunofluorescence staining. Using this position on the brain map of Nile grass rat, dorsal raphe nucleus (DRN) lesions were produced by microinjection of an adeno-associated virus (AAV) carrying diphtheria toxin-fragment A (DTA) or the serotonergic neuron toxin 5,7-dihydroxytryptamine (5,7-DHT). Spontaneous locomotor rhythms were monitored for 1 week following a recovery period. The 5,7-DHT lesions destroyed approximately 90 % of tryptophan hydroxylase 2-positive neurons in the DRN and chronically increased daytime activity in female Nile grass rats. The results are independent of estrous cycles because estrous cycles were paused in this species under male-isolated recording environments. AAV-DTA lesions, which were driven by nonspecific CMV-Cre, partially (<60 %) destroyed DRN serotonergic neurons but failed to modulate activity levels. Additionally, neither 5,7-DHT nor AAV-DTA modulated night-time activities. Interestingly, 5,7-DHT produced the same damage in DRN serotonergic neurons in male Nile grass rats but had little effect on their activity. Furthermore, the depression index, determined by a tail suspension test, was not modulated by DRN lesions regardless of the lesion method or sex of Nile grass rats. Previous studies showed that diurnal activity in Nile grass rats is highly dependent on light intensity. Thus, disinhibition of photic inputs by DRN lesions may be a plausible mechanism, although the underlying mechanisms require further investigation.