Male and Female Mice Enter Social Encounters with Different Brain States
The brain may begin preparing for a social encounter differently in males and females, long before another animal comes within sniffing distance. That is the striking implication of a new study in freely behaving mice, in which researchers recorded electrical activity simultaneously across several regions of the amygdalo-striatal network while the animals performed a series of social discrimination tasks. The work found sex-dependent patterns not only during direct interaction, but also in the neural activity that preceded it. The strongest and most consistent differences appeared in the basolateral amygdala, or BLA, a region that helps evaluate emotional significance, social cues and potential threats. The findings suggest that biological sex can shape the brain’s baseline operating state as well as its rapid response to changing social circumstances, offering a more detailed view of how social behaviour is assembled moment by moment in the mammalian brain.
Social behaviour is essential for survival in mice and many other mammals. Animals must recognize potential mates, distinguish familiar companions from strangers, assess danger, respond to distress and decide whether to approach, investigate or withdraw. These decisions are not controlled by a single “social centre” in the brain. Instead, they emerge from communication among distributed circuits that include the amygdala, which assigns emotional and motivational value to sensory information, and the striatum, which helps translate those signals into actions and reward-related decisions. Previous research has shown that males and females can differ in social behaviour and that genes and hormones influence these differences. Yet it has remained difficult to determine how sex affects the coordinated electrical dynamics of the brain during naturalistic encounters. Measuring one region at a time can miss the network-wide interactions through which social decisions are made.
To address that problem, Adèle Phalip, Shai Netser and Shlomo Wagner at the University of Haifa used chronically implanted electrode arrays to monitor extracellular neural activity in awake, freely moving mice. The electrodes allowed the researchers to record the electrical signals generated by populations of neurons across multiple amygdalo-striatal regions while the animals behaved without the restrictions imposed by anesthesia or head fixation. Neural recordings were synchronized with video-based tracking and measurements of head acceleration. This combination enabled the team to relate electrophysiological activity to specific phases of an encounter, including the moments before contact, the initial investigation of another mouse and the animals’ changing movement patterns. Rather than treating social behaviour as a single event, the approach examined it as a sequence of decisions and actions unfolding across time.
The mice completed four tasks designed to probe different dimensions of social discrimination. These included tests of preference for a social stimulus over a nonsocial one, preference involving an opposite-sex animal, responses to an isolated conspecific and reactions to a stressed conspecific. Such comparisons allowed the researchers to ask whether sex differences were general features of brain activity or whether they depended on the identity and condition of the animal being investigated. The design also made it possible to compare neural responses across different social contexts while tracking movement objectively. Head acceleration provided measures of how vigorously and dynamically the animals moved, helping distinguish activity associated with social processing from activity linked simply to locomotion or physical arousal.
The first major result emerged before social interaction began. Male and female mice displayed distinct neural activity patterns during the anticipatory period, when an animal was approaching or preparing to encounter a social stimulus but had not yet begun interacting. This indicates that sex-related differences are not limited to the brain’s reaction to another animal’s behaviour. Instead, the two groups may enter the encounter with different network states, potentially reflecting differences in expectation, motivation, arousal or the way incoming social information is evaluated. In technical terms, the baseline activity of the network was already organized differently before the social stimulus became behaviourally salient. Such anticipatory states could influence what happens next, because the same sensory cue may be processed differently depending on the circuit’s initial configuration.
During the encounters themselves, the differences were distributed across regions and across several features of the electrical signals. The researchers examined neural firing and local field potentials, which are slower voltage fluctuations that reflect the summed activity of nearby neural populations and synaptic inputs. Among the most robust distinctions involved high-frequency oscillations, or HFOs. These rapid fluctuations can provide a readout of local circuit engagement and the coordination of activity among neurons, although their precise cellular origins and functions can vary with brain region and behavioural state. The prominence of HFO differences across contexts suggests that sex may influence how local neural populations synchronize or process rapidly changing social information. Importantly, the pattern was not uniform across every region or every stage of an encounter, reinforcing the idea that sex-dependent neural dynamics are context-sensitive rather than a simple global increase or decrease in activity.
The basolateral amygdala stood out as the network’s most consistent site of sex-dependent activity. The BLA receives and integrates sensory information and is widely involved in assigning emotional value to stimuli, learning associations and selecting appropriate responses. During social interactions, BLA activity differed according to sex, social context and the timing of the encounter, with especially pronounced effects during its initial phase. The first moments of contact are often critical: a mouse must rapidly determine whether another animal is familiar, attractive, threatening, distressed or worth investigating. The study’s results suggest that the BLA may help generate sex-specific versions of this early social evaluation. Rather than operating as a fixed male-versus-female switch, however, the region appeared to change its activity according to when the interaction occurred and what kind of social stimulus was present.
The electrical signatures also tracked behaviour. Sex-specific BLA activity was associated with differences in movement dynamics while mice investigated isolated conspecifics. This relationship is important because it links neural activity to an observable response rather than describing sex differences as purely abstract patterns in a recording. A change in BLA oscillations could accompany a change in approach intensity, head movements or exploratory engagement, providing evidence that network dynamics are connected to the way animals physically respond to a social partner. At the same time, the association does not prove that BLA activity directly causes the behavioural difference. Neural activity and movement can influence one another, and both may be shaped by factors such as motivation, stress or hormonal state. The findings therefore identify a circuit relationship that can be tested in future experiments using causal techniques, such as targeted stimulation or inhibition of defined BLA pathways.
The study highlights why experiments that include both sexes and record across multiple brain regions can reveal patterns missed by narrower designs. A single measurement taken after an interaction might suggest that males and females differ in the magnitude of a response, while the present approach shows that the timing, frequency composition and network location of activity also matter. It further indicates that social neuroscience should pay attention to the period before an encounter, when expectations and internal states may already bias perception and action. Because the work was conducted in mice, it cannot establish that the same neural mechanisms operate in humans, and human social behaviour is shaped by additional developmental, cultural and cognitive influences. Nevertheless, the amygdala and striatal circuits are evolutionarily conserved, making the results relevant to basic questions about mammalian social processing.
The authors say the findings may eventually help guide research into psychiatric conditions in which social functioning is affected differently across sexes, including autism spectrum disorder and other disorders involving emotional regulation or social motivation. Any clinical connection remains a future possibility rather than a conclusion of the mouse study. The immediate advance is more fundamental: sex appears to shape both the brain state that precedes a social encounter and the changing electrical response that unfolds during it. By combining multi-site electrophysiology, local field potential analysis and detailed behavioural tracking, the researchers place the BLA at the centre of a dynamic network in which social meaning, movement and biological sex intersect. The result is a portrait of social behaviour not as a single response, but as a rapidly shifting conversation between brain regions whose opening signals may differ before the conversation even starts.
Subject of Research: Sex-dependent neural activity in the amygdalo-striatal network during social behaviour in freely behaving mice
Subject of Research: Medicine
Article Title: Sex differences in neural activity across amygdalo-striatal network during social behaviour
Article References: Phalip, A., Netser, S. & Wagner, S. “Sex differences in neural activity across amygdalo-striatal network during social behaviour.” Biology of Sex Differences
Image Credits: AI Generated
DOI: 10.1186/s13293-026-00969-8
Keywords: sex differences, mouse social behaviour, amygdalo-striatal network, basolateral amygdala, brain-wide electrophysiology, multielectrode arrays, high-frequency oscillations, social neuroscience
Tags: amygdalo-striatal network in social behaviorbasolateral amygdala and social cuesbasolateral amygdala functionbiological sex influence on brain functionbrain activity before social interactionselectrophysiological brain recordingsemotional evaluation in social encountersemotional processing in mammalsinfluence of biological sex on neural responsesmammalian social decision-makingneural basis of social behavior in miceneural basis of social interactionsneural circuits in social behaviorneural mechanisms of social decision-makingneural response to social threatspre-encounter brain statespre-social encounter brain statessex differences in amygdala-striatal activitysex-dependent brain activitysex-dependent neural patterns in mammalssocial behavior in micesocial discrimination taskssocial discrimination tasks in mice
