Pubertal sex hormones control transcriptional trajectories in the medial preoptic area

Hashikawa, Koichi; Hashikawa, Yoshiko; Liu, Yuejia; Rossi, Mark A.; Basiri, Marcus L.; Chen, Jane; Ahmad, Omar R.; Mukundan, R.; Johnston, Nathan L.; McHenry, Jenna A.; Palmiter, Richard D.; Rubinow, David R.; Zweifel, Larry S.; Stuber, Garret D.

doi:10.1101/2021.09.02.458782

Cited by 4 publications

(7 citation statements)

References 113 publications

(243 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

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

Ottenheimer,

Simon,

Burke

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

The ventral pallidum (VP) was defined as a basal ganglia nucleus with dense input from ventral striatum. To further investigate a VP regional identity, we conducted a cross-species transcriptional characterization of VP cell types. We performed single nucleus RNA-sequencing of VP tissue from mice and rats and identified 16 VP neuronal subclasses with striking cross-species conservation. VP GABAergic neurons were surprisingly heterogeneous, consisting of 14 sub-classes from 3 developmental classes. Combining our sequencing data with a spatial atlas revealed that all VP subclasses extended beyond the traditional borders of VP. Integrating our VP data with prior sequencing data from striatal, hypothalamic, and extended amygdalar tissue confirmed that cell types are shared among these regions. Due to the role of VP in feeding behavior, we also assessed the transcriptional impact of high-fat diet consumption, which induced altered expression of genes involved in oxidative phosphorylation and inhibitory signaling. Overall, our results demonstrate that VP is not a transcriptionally discrete nucleus; rather, VP contains cell types with diverse expression patterns that overlap with regions beyond the basal ganglia.

show abstract

Section: Resultsmentioning

confidence: 99%

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

Section: Methodsmentioning

confidence: 99%

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

Ottenheimer,

Simon,

Burke

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…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.…”

Section: Resultsmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Ishii,

Hashikawa,

Chea

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

SUMMARYThe completion of mating acutely suppresses sexual motivation in male mice. In contrast, relatively little is known about how the completion of mating affects sexual motivation and sexual behavior in female mice. How the brain responds to completion of mating is also unclear. Here, by using self-paced mating assay, we first demonstrate that female mice show decreased sexual motivation after the completion of mating. By using brain-wide analysis of activity-dependent labeling, we next pin-pointed the medial preoptic area as a brain region strongly responding to mating completion. Furthermore, using freely movingin vivocalcium imaging to compare neural activity of inhibitory and excitatory neurons in the medial preoptic area, we revealed that a subset of neurons responds significantly and specifically to mating completion but not to appetitive or consummatory behaviors. While there were excitatory and inhibitory neurons that showed positive response to the completion of mating, the response magnitude as well as the proportion of neurons responding to the event was significantly larger in the inhibitory neuron population. Next, by unbiased classification of their responses, we also found a subpopulation of neurons that increase their activity late after the onset of the completion of mating. These neurons were all inhibitory indicating that the completion of mating induces a prolonged inhibitory activity in the medial preoptic area. Lastly, we found that chemogenetic activation of medial preoptic area neurons that respond to mating completion, but not to appetitive behaviors, was sufficient to suppress female sexual motivation. Together, our data illuminate the importance of medial preoptic area as a brain node which encodes a negative signal that sustains low sexual motivation state after the completion of mating in female mice.HighlightsFemale mice show decreased sexual motivation after mating completion.A subset of MPOA neurons respond specifically to mating completion.Mating completion evokes persistent activity in MPOA inhibitory neurons.Activation of a subset of MPOA neurons is sufficient to suppress female sexual motivation.

show abstract

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Nishiike,

Okubo

2024

Preprint

View full text Add to dashboard Cite

Adult male animals typically court and attempt to mate with females, while attacking other males. Emerging evidence from mice indicates that neurons expressing the estrogen receptor ESR1 in behaviorally relevant brain regions play a central role in mediating these mutually exclusive behavioral responses to conspecifics. However, the findings in mice are unlikely to apply to most other vertebrates, where androgens, rather than estrogens, have been implicated in male behaviors. Here we report that male medaka (Oryzias latipes) lacking one of the two androgen receptor subtypes (Ara) are less aggressive toward other males and instead actively court them, while those lacking the other subtype (Arb) are less motivated to mate with females and conversely attack them. These findings indicate that, in male medaka, the Ara- and Arb-mediated androgen signaling pathways facilitate appropriate behavioral responses, while simultaneously suppressing inappropriate responses, to males and females, respectively. Notably, males lacking either receptor retain the ability to discriminate the sex of conspecifics, suggesting a defect in the subsequent decision-making process to mate or fight. We further show that Ara and Arb are expressed in intermingled but largely distinct populations of neurons, and stimulate the expression of different behaviorally relevant genes including galanin and vasotocin, respectively. Collectively, our results demonstrate that male teleosts make adaptive decisions to mate or fight as a result of the activation of one of two complementary androgen signaling pathways, depending on the sex of the conspecific that they encounter.

show abstract

Pubertal sex hormones control transcriptional trajectories in the medial preoptic area

Cited by 4 publications

References 113 publications

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

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

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

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

Contact Info

Product

Resources

About