A neural circuit for male sexual behavior and reward

Bayless, Daniel W.; Davis, Chung-ha O.; Yang, Renzhi; Wei, Yichao; de Andrade Carvalho, Vinicius Miessler; Knoedler, Joseph R.; Yang, Taehong; Livingston, Oscar; Lomvardas, Akira; Martins, Gabriela J.; Vicente, Ana Mafalda; Ding, Jun B.; Luo, Liqun; Shah, Nirao M.

doi:10.1016/j.cell.2023.07.021

Cited by 19 publications

(9 citation statements)

References 118 publications

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“…The neural mechanisms that regulate the sequential transitions of male copulatory behaviours, such as mounting, intromission, and ejaculation, remain unclear. Previous studies have identified specific brain regions that control mounting 8–11 , but the brain regions that regulate intromission and ejaculation are to be elucidated. Here, we identified the vsNAc as a critical brain region where dual ACh-DA dynamics aligned with and coordinate the sequential transitions from intromission to ejaculation.…”

Section: Discussionmentioning

confidence: 99%

“…All AAVs were prepared at the University of Tsukuba. AAV titres were 9.79 × 10 11 – 6.24 × 10 14 genomic copies/mL.…”

Section: Methodsmentioning

confidence: 99%

“…For example, the nucleus accumbens (NAc) is thought to be involved in courtship behaviours, whereas the preoptic area (POA) has been implicated in copulatory behaviours 1,6 . However, recent studies indicated that POA primarily controls mounting 8–11 . Thus, the specific brain regions that regulate intromission and ejaculation are not yet identified, which hinders our understanding of the neural basis for controlling the intromission-to-ejaculation transition.…”

Section: Introductionmentioning

confidence: 99%

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Sequential Transitions of Male Sexual Behaviors Driven by Dual Acetylcholine-Dopamine Dynamics

Miyasaka,

Kanda,

Nonaka

et al. 2023

Preprint

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In mammals, males execute a stereotypical and organized sequence of sexual behaviours, such as mounting, intromission, and ejaculation, to successfully complete copulation. However, the neural mechanisms that govern the sequential transitions of male copulatory behaviours remain unclear. Here, we report that dopamine (DA) and acetylcholine (ACh) dynamics in the ventral shell of the nucleus accumbens (vsNAc) closely align with serial transitions of sexual behaviours in male mice. In particular, the vsNAc exhibits a unique pattern of 1.5–2.2 Hz dual ACh-DA rhythms that correspond to the pelvic thrust rhythm during intromission. The dual ACh-DA rhythms are generated locally by reciprocal regulation between ACh and DA signalling via nicotinic acetylcholine (nAChR) and dopamine D2 (D2R) receptors, respectively. Knockdown of choline acetyltransferase (ChAT) and D2R expression in the vsNAc diminishes intromission and ejaculation. We showed that ACh signalling promotes the initiation of intromission, whereas DA signalling sustains intromission by inhibiting the activities of D2R-expressing neurons in the vsNAc. Moreover, optogenetic activation of ChATvsNAcneurons during intromission slows down the DA rhythm, a specific activity signature that precedes ejaculation, and leads to immediate ejaculation. Taken together, dual ACh-DA dynamics in the vsNAc coordinate sequential transitions of male copulatory behaviours from intromission to ejaculation.

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Section: Discussionmentioning

confidence: 99%

“…All AAVs were prepared at the University of Tsukuba. AAV titres were 9.79 × 10 11 – 6.24 × 10 14 genomic copies/mL.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sequential Transitions of Male Sexual Behaviors Driven by Dual Acetylcholine-Dopamine Dynamics

Miyasaka,

Kanda,

Nonaka

et al. 2023

Preprint

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“…Moreover, the strategies used to develop such indicators were applied to expand the repertoire of ligands that can be detected (Figure 1). GPCR‐based GEFIs have been used to study a wide range of behaviors/diseases that include but are not limited to addiction (Luján et al., 2023), anxiety fear memory (Ji et al., 2023), motor memory (Linders et al., 2022; Mineur et al., 2022), Parkinson's disease (Alhadeff et al., 2019; Lin et al., 2021), sexual drive/reproduction (Bayless et al., 2023), sleep (Dong et al., 2019), and social interaction (Hu et al., 2021) (For complete list of publications and details see Table S1). This review aimed to showcase the applicability, diversity, and flexibility and to highlight the performance and tolerability of such tools.…”

Section: Indicator Applicationsmentioning

confidence: 99%

Engineering, applications, and future perspectives of GPCR‐based genetically encoded fluorescent indicators for neuromodulators

Rohner,

Lamothe‐Molina,

Patriarchi

2024

Journal of Neurochemistry

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This review explores the evolving landscape of G‐protein‐coupled receptor (GPCR)‐based genetically encoded fluorescent indicators (GEFIs), with a focus on their development, structural components, engineering strategies, and applications. We highlight the unique features of this indicator class, emphasizing the importance of both the sensing domain (GPCR structure and activation mechanism) and the reporting domain (circularly permuted fluorescent protein (cpFP) structure and fluorescence modulation). Further, we discuss indicator engineering approaches, including the selection of suitable cpFPs and expression systems. Additionally, we showcase the diversity and flexibility of their application by presenting a summary of studies where such indicators were used. Along with all the advantages, we also focus on the current limitations as well as common misconceptions that arise when using these indicators. Finally, we discuss future directions in indicator engineering, including strategies for screening with increased throughput, optimization of the ligand‐binding properties, structural insights, and spectral diversity.

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“…While courting a mate increases the chances of reproductive success, it also carries risks, such as exposure to predation. Recent work has revealed how sex drive and threat avoidance are independently signaled in the brain 14–22 ,yet it remains unclear how these needs are prioritized when they are in conflict. Avoiding threats can be a life-saving decision, but excessive caution might result in missed mating opportunities.…”

Section: Mainmentioning

confidence: 99%

Mating proximity blinds threat perception.

Cazale Debat,

Scheunemann,

Day

et al. 2024

Preprint

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Romantic engagement can bias sensory perception. This 'love blindness' reflects a common behavioral principle across organisms: favoring pursuit of a coveted reward over potential risks. In the case of animal courtship, such sensory biases may support reproductive success but can also expose individuals to danger, such as predation. How do neural networks balance the trade-off between risk and reward? Here, we discover a dopamine-governed filter mechanism in male Drosophila that reduces threat perception as courtship progresses. We show that during early courtship stages, threat-activated visual neurons inhibit central courtship nodes via specific serotonergic neurons. This serotonergic inhibition prompts flies to abort courtship when they see imminent danger. However, as flies advance in the courtship process, the dopaminergic filter system reduces visual threat responses, shifting the balance from survival to mating. By recording neural activity from males as they approach mating, we demonstrate that progress in courtship is registered as dopaminergic activity levels ramping up. This dopamine signaling inhibits the visual threat detection pathway via Dop2R receptors, allowing male flies to focus on courtship when they are close to copulation. Thus, dopamine signaling biases sensory perception based on perceived goal proximity, in order to prioritize between competing behaviors.

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A neural circuit for male sexual behavior and reward

Cited by 19 publications

References 118 publications

Sequential Transitions of Male Sexual Behaviors Driven by Dual Acetylcholine-Dopamine Dynamics

Sequential Transitions of Male Sexual Behaviors Driven by Dual Acetylcholine-Dopamine Dynamics

Engineering, applications, and future perspectives of GPCR‐based genetically encoded fluorescent indicators for neuromodulators

Mating proximity blinds threat perception.

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