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New Neural Circuit Discovered: The Secret Behind Choosing to Have More or Fewer Friends


Scientists have discovered a part of the brain responsible for making mice prefer to live in larger groups. The study showed that communication between two regions of the brain, the anterior cingulate cortex (ACC) and the lateral septum (LS), influences this social preference. When the researchers turned off this circuit, male mice began to prefer smaller groups, while females showed no clear choice.


For many species, including humans, environmental conditions have made living in large groups an advantage. Being in larger groups offers many benefits, such as traveling together, having less risk of attack by predators, increasing the chance of survival of offspring, and improving body balance.


For this reason, this behavior has evolved several times in different types of animals, such as insects, bird,s and mammals. Understanding how the brain makes mammals join together in groups is a challenge that many scientists are trying to solve.


An area of ​​the brain called the lateral septum (LS) is increasingly being shown to be important for social behaviors and may play a key role in group living.


In the past, the LS was mainly known for being involved in “septal rage,” as it was associated with aggression in rats and mice. However, more recent studies have shown that the LS has a more complex function, helping these animals recognize each other and encouraging positive social behaviors in species such as voles and some birds.


The LS (lateral septum) receives signals from multiple parts of the brain, which puts it in a unique position to process sensory information important for group interactions and then coordinate appropriate social responses to the environment.

Information about social behavior can come from cortical regions of the brain, as shown in studies of bats, which revealed unique neural patterns for identifying specific individuals within family groups.


In addition, the anterior cingulate cortex (ACC), a part of the brain linked to complex behaviors such as empathy, also plays an important role in group living.


This brain circuit appears to help animals live in large groups, controlling not only sociability but also inhibiting aggression, which would be common in many contexts.


For example, the LS, which is made up mainly of inhibitory (GABAergic) neurons, can reduce the activity of areas of the brain that promote aggression, such as the lateral hypothalamus. This facilitates positive social interactions and helps different animals live in large groups, even in situations where they might otherwise be aggressive.

Model by which the lateral septum (LS) contributes to the regulation of nucleus accumbens (NA) function. The LS is a convergence point for dopaminergic input from the ventral tegmental area (VTA) and (putatively) glutamatergic input from the medial prefrontal cortex (mPFC), both of which may regulate their GABA release into the NA. GABA levels released into the NA by LS afferents in turn regulate their activity, such as through the regulation of dopamine levels in the NA. This figure was uploaded by Robert Andrew Chambers. DOI: 10.1016/j.brainresrev.2004.04.009


Studying how mammals group together is a major challenge, largely because suitable animal models are lacking in the laboratory. Many of the animals used in research have not evolved to naturally live in large groups.


However, scientists at Emory University have discovered an interesting solution: spiny mice of the genus Acomys. In their field studies, they have observed that these mice live in mixed-sex groups ranging in size from 12 to 46 individuals.


In food-rich environments, these groups can grow even larger. In the laboratory, both males and females of one species, Acomys dimidiatus (formerly known as Acomys cahirinus), can be successfully raised in single-sex groups of up to 30 individuals, which allows for the study of social behaviors outside of the context of reproduction.


Unlike other laboratory mammals, these spiny mice are extremely sociable, showing little aggression, and they get along well with others, regardless of age, familiarity, or kinship.


They also prefer to be in larger groups and readily accept new members into established groups. These characteristics make spiny mice an ideal model for studying how the brain adapts to support social behaviors, such as grouping, that are essential for the formation of more complex societies, such as those we see in humans and other cooperative animals.

Spiny mice of the genus Acomys


In the current study, the researchers wanted to understand which brain circuitry underlies the spiny mice’s preference for larger groups. To do this, they conducted an experiment in which they exposed some mice to smaller groups and others to larger groups.


Then, they scanned the animals’ brains for the protein Fos, which is produced when neurons are active. The results showed that activity in the lateral septum (LS), a brain region linked to social behavior, was significantly higher in the mice that preferred larger groups. This suggests that the LS may be a key player in controlling this preference for sociability in large groups.


To better understand the brain circuitry linked to the preference for larger groups, the researchers repeated the previous experiment, but this time they added neuronal markers to the mice.


These chemical probes allowed them to map the origin and path of the signals in the brain. The results showed that spiny mice that preferred larger groups had stronger communication between the anterior cingulate cortex (ACC) and the lateral septum (LS).


The ACC has been linked to social behaviors, such as comfort, in other animals, and in humans, it is involved in processes such as attention, decision-making,g, and emotions.


To test the impact of this circuit, the scientists used chemogenetic tools that allowed them to temporarily "turn off" the pathway between the ACC and the LS.


The result was intriguing: in females, turning off the circuit caused them to lose their preference for larger groups. Males, on the other hand, began to prefer smaller groups, an unexpected behavior change.


According to one of the researchers, Fricker, the impact was surprising: "This shows that the ACC-LS circuit has a strong influence on group size preference."


The researchers also wanted to see whether the ACC-LS circuit was specific to social preferences or whether it influenced any type of group preference, even with inanimate objects.


To do this, they experimented with rubber ducks. The spiny mice, which typically prefer to explore a larger group of ducks rather than a smaller one, showed no change in this preference when their brain circuitry was manipulated.


This indicated that the ACC-LS circuit specifically regulates social behavior and preference for groups of other mice, rather than inanimate objects. As Fricker explained, “This showed that the neural circuitry we identified is modulating social group size preferences, rather than a more general preference.” Now, the researchers are ready to further investigate mammalian social behavior, using spiny mice as a model.


According to Kelly, the next step is to collect more behavioral data by allowing the mice to interact in large groups while monitoring their brain activity. This will help us understand how neural activity relates to complex and changing social behaviors. Among the next challenges Kelly wants to explore are the factors that facilitate group cooperation and the environmental conditions that can cause groups to disband and lead to more selfish behavior.



READ MORE:


Cingulate to septal circuitry facilitates the preference to affiliate with large peer groups

Brandon A. Fricker,  Malavika Murugan, Ashley W. Seifert,  Aubrey M. Kelly

Current Biology. Published online September 11, 2024

DOI: 10.1016/j.cub.2024.08.019


Abstract:


Despite the prevalence of large-group living across the animal kingdom, no studies have examined the neural mechanisms that make group living possible. Spiny mice, Acomys, have evolved to live in large groups and exhibit a preference to affiliate with large over small groups. Here, we determine the neural circuitry that facilitates the drive to affiliate with large groups. We first identify an anterior cingulate cortex (ACC) to lateral septum (LS) circuit that is more responsive to large than small groups of novel same-sex peers. Using chemogenetics, we then demonstrate that this circuit is necessary for both male and female group investigation preferences but only for males’ preference to affiliate with larger peer groups. Furthermore, inhibition of the ACC-LS circuit specifically impairs social, but not nonsocial, affiliative grouping preferences. These findings reveal a key circuit for the regulation of mammalian peer group affiliation.


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