Timing is everything when trying to land a mate. In many species, female receptivity to male sexual advances is synchronized to fertility and is mediated by steroid hormones produced in the gonads, such as oestrogens. How these hormones tune neural circuits to transition females to mate-seeking mode is unclear. In a series of elegant experiments, neuroscientist Jenna McHenry and colleagues in Garret Stuber's laboratory at the University of North Carolina at Chapel Hill, USA, investigated a hormone-responsive neural circuit important for mate attraction in female mice.
The medial preoptic area in the brain controls a range of social and sexual behaviours. McHenry focused on cells containing the reward-associated peptide neurotensin. Neurotensin-expressing cells make up nearly one-third of all input to the ventral tegmental area of the brain, which produces the pleasure-associated neurotransmitter dopamine, making it likely that the neurotensin-expressing cells mediate reinforcement of social behaviour.
To determine the sensory input that activates neurotensin-producing neurones, McHenry constructed mice that emit light in the medial preoptic area every time Ca2+ is released as an indicator of neural activity. McHenry then ‘perfumed’ female mice with male or female urine while measuring the amount of light emitted by the neurotensin-producing cells. They discovered that a large group of neurones was excited by the male scent (37%), while only a small number of cells responded to female odours (8%). Neurotensin-producing cells in the medial preoptic area of the brain are turned on by social cues and the team also showed that social excitement is amplified by steroid hormones. But the behavioural consequences of activating these cells were still not clear.
To get at the behavioural function, McHenry developed a new set of mice with special light-gated neurotensin neurones. Unlike the mice used previously that emitted light from active neurones, these mice had light-activated neurones. Specifically, McHenry expressed light-gated Na+ channels in neurotensin-expressing cells, so that every time she artificially flashed a light pulse in the brain, these photoreceptive neurones perceived the light and Na+ channels rapidly opened, leading to neural activation. McHenry implanted fibre optic cables into the medial preoptic area to provide a light source, and monitored how rewarding it was for mice to stimulate these light-sensitive neurotensin-producing cells by seeing how often mice chose to activate these cells. McHenry found that mice activated these cells across all phases of the female's fertility cycle, but activated them the most when oestradiol levels were highest, suggesting that natural rises in oestradiol activate oestrogen receptors in neurotensin-producing neurones, leading to an increase in mate seeking coincident with peak fertility. However, McHenry was still in the dark about how medial preoptic activation changed the brain.
The team posited that the medial preoptic area controls dopamine release in the downstream ventral tegmental area of the brain. As most of the neurotensin-producing cells in the medial preoptic area that signal to the ventral tegmental area of the brain inhibit neural activity, the team suspected that they may silence cells in the ventral tegmental area and release the brakes on dopamine production, making the experience pleasurable. To test this, McHenry activated the medial preoptic area cells and simultaneously measured dopamine levels in the downstream nucleus accumbens brain region. She found that activating the medial preoptic area ramped up dopamine levels in the nucleus accumbens, especially in oestradiol-primed mice. Thus, the medial preoptic area enables mate seeking by increasing dopamine in reward-related brain regions such as the nucleus accumbens.
In short, McHenry and colleagues’ study has illuminated the role of a specific brain circuit that enables mate seeking and sheds mood-light on how these hormone-sensitive cells scent the stage for finding love at the right time.