
The sociosexual preference of mice is modulated by a complex interaction between innate needs and external threats, mediated by brain circuits that regulate dopamine release. This study therefore introduces a neural mechanism to understand how social decisions can be convergently determined by the balance between innate requirements and external threats to survival.
Sociosexual behavior refers to social interactions between individuals of different sexes, which are fundamental for processes such as mating and reproduction. In addition to these interactions, there are also important relationships between individuals of the same sex, which provide social support and collaboration.
The way in which animals choose who to interact with, especially in situations of threat, is influenced by both innate needs and the external environment. However, the brain mechanisms that regulate these decisions are still not fully understood.

Researchers at Xi’an Jiaotong University investigated how male and female mice choose between interactions with other males or females in normal situations and under external threat.
The study focused on the ventral tegmental area (VTA) of the brain, where dopaminergic neurons (VTADA neurons) play a crucial role in modulating these preferences.
The activity of the neurons was monitored using two-color fiber photometry, a technique that measures calcium levels, an indicator of neuronal activity.

The image above shows an example of a neuronal movie created using calcium imaging. Source: Professor Dorit Hochbaum. UC Berkeley
They also used Chemogenetic and Optogenetic manipulations. These techniques allowed the scientists to control the activity of VTADA neurons. Chemogenetics involves using chemicals to activate or inhibit specific neurons, while optogenetics uses light for the same purpose.
To study the responses to threats, the mice were exposed to different threats, such as predator odors (trimethylthiazoline - TMT), visual and auditory fear conditioning, to simulate risky situations.

Wireless optogenetic tools like these tiny implants in living mice are allowing scientists to map the stimulation of certain neurons in the brain to specific responses. SOURCE: J. Rogers/Northwestern Univ.
The results show that both males and females prefer interactions with females under normal conditions.
When exposed to threats, both sexes changed their preference to interact with males. This suggests that social decisions can be adjusted in response to external dangers.
Activation of dopamine neurons in the ventral tegmental area correlated with the change in sexual preference under stress. When these neurons were chemogenetically activated, preference for males increased; when they were inhibited, the response to TMT was blocked, confirming the role of these neurons in the preference shift.
Projection from VTADA neurons to different brain areas, such as the nucleus accumbens (NAc) and the medial preoptic area (mPOA), showed distinct patterns in males and females.
In males, female preference was promoted under normal conditions by NAc activity, whereas threats increased activity in the mPOA, promoting male preference. In females, the firing pattern of neurons to the NAc determined sexual preference.

Sexually dimorphic dopamine circuits determine sociosexual preference. Males use competition between the VTADA-NAc projection pathways (promoting female preference) and the VTADA-mPOA projection pathways (promoting male preference under survival stress) to determine their social decisions. Conversely, altered VTADA-NAc projection firing patterns are used by females to determine their sociosexual preferences, mediating female preference via dopamine type 1 receptor (DA-D1R) transmission dominated by phasic firing and male preference via dopamine type 2 receptor (DA-D2R) transmission facilitated by tonic firing under survival stress. nucleus accumbens (NAc). medial preoptic area (mPOA)
Dopamine release varied between the sexes. In males, sustained dopamine release in response to threats led to male preference.
In females, faster and more intense dopamine release promoted female preference.
This study reveals how the interplay between neural circuits, neurotransmitters and environmental contexts can influence social decisions. Sociosexual preference in mice is modulated by a complex interplay between innate needs and external threats, mediated by brain circuits that regulate dopamine release, shaping social behavior in a sexually dimorphic manner.
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Sexually dimorphic dopaminergic circuits determine sex preference
Anqi Wei et al. ,
Science, VOL. 387, NO. 6730, (2025).
DOI:10.1126/science.adq7001
Abstract:
Sociosexual preference is critical for reproduction and survival. However, neural mechanisms encoding social decisions on sex preference remain unclear. In this study, we show that both male and female mice exhibit female preference but shift to male preference when facing survival threats; their preference is mediated by the dimorphic changes in the excitability of ventral tegmental area dopaminergic (VTADA) neurons. In males, VTADA projections to the nucleus accumbens (NAc) mediate female preference, and those to the medial preoptic area mediate male preference. In females, firing-pattern (phasic-like versus tonic-like) alteration of the VTADA-NAc projection determines sociosexual preferences. These findings define VTADA neurons as a key node for social decision-making and reveal the sexually dimorphic DA circuit mechanisms underlying sociosexual preference.
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