Serotonergic projections from the caudal raphe nuclei to the hypoglossal nucleus in male and female rats

The respiratory control system is sexually dimorphic. In many brain regions, including respiratory motor nuclei, serotonin (5HT) levels are higher in females than in males. We hypothesized that there could be sex differences in 5HT input to the hypoglossal nucleus, a region of the brainstem involved in upper airway control. Adult Fischer 344 rats were anesthetized and a retrograde transsynaptic neuroanatomical tracer, Bartha pseudorabies virus (PRV), was injected into the tongue. Sections through the medulla were reacted immunocytochemically for the presence of (i) PRV, (ii) tryptophan hydroxylase (TPH; marker of 5HT neurons), (iii) PRV combined with TPH, and (iv) 5HT. Sex hormone levels were measured in female rats and correlated with TPH immunoreactivity, as hypoglossal 5HT levels vary with the estrous cycle. The number of PRV neurons was comparable in male and female rats. The number and distribution of TPH immunoreactive neurons in the caudal raphe nuclei were similar in male and female rats. The subset of 5HT neurons that innervate hypoglossal motoneurons was also similar in male and female rats. With the exception of the ventrolateral region of the hypoglossal nucleus, 5HT immunoreactivity was similar in male and female rats. These data suggest that sex differences in 5HT modulation of hypoglossal motoneurons in male and female rats are not the result of sex differences in TPH or 5HT, but may result from differences in neurotransmitter release and reuptake, location of 5HT synaptic terminals on hypoglossal motoneurons, pre- and postsynaptic 5HT receptor expression, or the distribution of sex hormone receptors on hypoglossal or caudal raphe neurons.