Pubertal sex hormones control transcriptional trajectories in the medial preoptic area

Abstract

Pubertal maturation aids development of emotion, cognition, and reproduction. We investigated transcriptional dynamics in the medial preoptic area (MPOA), a hypothalamic center for reproductive behaviors, in male and female mice at single-cell resolution (scRNAseq) during puberty. Defined subsets of neurons expressing Slc32a1 and Esr1 (Vgat+ Esr1+) were the most transcriptionally dynamic compared to other cell types throughout puberty. These cell type specific transcriptional progressions towards adulthood were bidirectionally controlled by the levels of circulating testosterone and estradiol. Selective deletion of Esr1 in Slc32a1-expressing cells in the MPOA prior to puberty arrested transcriptional progression and revealed a sexually dimorphic gene-regulatory network governed by Esr1. Deletion of Esr1 in Vgat+ cells prevented the development of mating behavior in both sexes. These analyses reveal both sexually common and dimorphic transcriptional progressions during puberty as well as their regulatory mechanisms, which have important implications towards understanding adaptative and maladaptive processes governing adolescent brain development.

Single-cell sequencing of rodent ventral pallidum reveals diverse neuronal subtypes with non-canonical interregional continuity

“…This observation introduced an unexplored possibility that VP contains neuronal populations that are transcriptionally continuous with nearby regions. We assessed this by integrating our VP neurons with neurons from NAc (as above), BNST ( n = 1, 936) ( 29 ), and POA ( n = 9, 807) ( 30 ) (Fig. 2G).…”

“…S2). We followed the same procedure to identify neurons in datasets from NAc ( 28 ), BNST ( 29 ), POA ( 30 ), and PAL ( 25 ).…”

Post-Mating Inhibition of Female Sexual Drive via Heterogeneous Neuronal Ensembles in the Medial Preoptic Area

“…MPOA is a molecularly heterogenous brain region. The area is a mixture of 80% inhibitory neurons and 20% of excitatory neurons which can be further classified into neuronal subtypes by marker gene expressions (Hashikawa et al, 2021; Moffitt et al, 2018). These subtypes are often associated with a biological function.…”

“…The medial preoptic area (MPOA), a molecularly and functionally heterogenous brain region, has classically been known to regulate wide variety of social behaviors (Fang et al, 2018; Hashikawa et al, 2021; Karigo et al, 2021; Kohl et al, 2018; Moffitt et al, 2018; Tsuneoka and Funato, 2021; Wei et al, 2018). Indeed, the MPOA has also been described to be an important brain area for the regulation of, including female sexual behavior.…”

The decision of male medaka to mate or fight depends on two complementary androgen signaling pathways

“…Nevertheless, the specific role of estrogen/ESR1 signaling in these neurons is still unclear. It has been consistently shown in rodents that estrogen/ESR1 signaling is essential for male behaviors (7)(8)(9). Specifically, testosterone secreted from the fetal testis is converted to estradiol-17β (E2) in the developing brain, which then acts through ESR1 to organize the neural substrates that later mediate male-typical behaviors.…”