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Stop, evaluate, and listen - serotonin surges when a female is present

A brain region involved in hearing surges with serotonin in male mice when a female is present but drops if the mouse is romantically rejected.

image alt text Fig.1 Mice are keenly aware when they’re not desired. Photograph by George Shuklin, distributed under a CC-BY 2.0 license

A recent study finds that male mice are keenly aware of being rejected [1].

“Read the room” is an informal way to tell your awkward friend “understand and respond accordingly to the current social context”. Easier said than done. And for most people, this occurs mostly unconsciously. But how exactly do we know when and how to respond to a given social situation? We listen.

To study how our brains hear in social situations, songbirds have become a popular animal model. As the name implies, songbirds rely heavily on hearing things to communicate, such as song, as well as other important vocal signals (e.g. food begging calls from their offspring).

Previous work [2] in zebra finches, an Australian songbird, found that estradiol (E2; a type of estrogen hormone) in auditory brain regions of males were rapidly increased in the presence of females. A subsequent study [3] found that this socially-induced boost in E2 enhances hearing-related brain activity (in this case, song).

But E2 isn’t the only chemical that rises when a female is present. Serotonin (abbreviated 5HT, for “5-hydroxytryptamine”), is a brain chemical that plays a diverse role in behavior, including a crucial role in helping the brain evaluate and respond to social cues, such as vocalizations.

Recently [1], Indiana University neuroscientist Laura Hurley and colleagues explored how serotonin changes in response to social situations using an electrochemical technique called voltammetry. Voltammetry is a highly precise and rapid method that quickly measures changing serotonin levels within discrete brain regions based on the change in local electrical current.

By placing an electrode into the inferior colliculus (IC; a brain region involved in hearing and processing social vocalizations; Fig. 2), the researchers could peer in to how levels of serotonin changed in male mice’s brain when a female was placed in an adjacent cage for 30 mins.

Fig. 2 Hearing pathway - from the ear to the brain (image from the University of Edinburgh Scottish Sensory Centre)

The findings reveal that just as E2 in the brains of zebra finches, 5HT rapidly increases in the IC of males by nearly 20% during social encounters and is specific to the female mouse being around (**Fig. 3**). Quickly after researchers removed the adjacent female, 5HT dropped by ~15%. So 5HT in the brain of male mice is linked to social context, in this case presence of Minnie Mouse. But what is serotonin’s function?

Fig.3 The rise and fall of serotonin during courtship. Figure adapted from [1].

One thought is that 5HT in IC, a key auditory processing brain region, may enhance male mice’s ability to hear themselves or their newly placed female neighbor. Just like two people on a (good) first date, rodent social encounters are marked by lots of chatting. Male mice produce what’s called “ultrasonic vocalizations” (USVs) to court a female mouse. As such, the researchers reasoned that loquacious males might have accordingly higher 5HT in the IC.

No such luck – irrespective of how Hurley and colleagues looked at the USV data, it appears that the amount of singing a bachelor mouse produced was independent of the 5HT in his brain. However, females also produce vocal communication signals called “squeaks” that often indicate aggression and/or rejection of a courting male. When researchers looked at the relationship between how often a female emitted a “squeak” to the level of 5HT, they found that the more a female rejected a male, the less 5HT was present in the male’s brain.

One interpretation might be that the more a courting male hears “No way!” from a potential mate, the less important it becomes to keep up his enhanced brain processing of vocal signals (since it’s just going to be rejection and heart-break again, sigh).

So while it might be emotionally hard to hear your crush reject you, it looks like the brain may have developed a way to soften the blow by ramping down serotonin levels, and in turn, reducing the painful auditory input.

References:

[1] Keesom, S. M. & Hurley, L. M. “Socially induced serotonergic fluctuations in the male auditory midbrain correlate with female behavior during courtship”. J. Neurophysiol. jn.00742.2015 (2016). doi:10.1152/jn.00742.2015. Link.

[2] Remage-Healey, L., Maidment, N.T. & Schlinger, B.A. “Forebrain steroid levels fluctuate rapidly during social interactions”. Nat Neurosci 11, 1327–1334 (2008). Link.

[3] Remage-Healey, L., Coleman, M.J., Oyama, R.K. & Schlinger, B.A. “Brain estrogens rapidly strengthen auditory encoding and guide song preference in a songbird”. Proc Natl Acad Sci U S A 107, 3852–3857 (2010). Link.

Related Links of Interest/Additional Material

Podcast interview with Sara Keesom and Laura Hurley about their paper in Journal of Neurophysiology:


An earlier version of this article originally appeared here.

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