Green-colored axonal projections from neurons with blue-colored nucelli flank a central oblong blue shape, creating a butterfly-like look.

Axonal projections from GABAergic neurons extend from the medial amygdala to hypothalamic areas of the brain to create a neuronal circuit that controls positive and negative social experiences in mice. In this image, axonal projections are shown in green

Credit: Weizhe Hong

Sociable circuits

A neural circuit responsible for the social reward response unravels the mystery of what drives human sociality.
Angela Zhang, PhD Headshot
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In human society, relationships are both rewarding and essential to everyday life, yet how the brain makes connections that establish relationships remains a mystery. Weizhe Hong, a neuroscientist at the University of California, Los Angeles, studies how the brain regulates social behavior from molecules to circuits. 

Hong’s recent paper in Nature Neuroscience describes a newly discovered neural circuit underlying social reward in mice. This circuit positively reinforces social interactions and when activated, can even overcome behavior associated with negative experiences, making it crucial for future studies of social impairments in neurodevelopmental and neuropsychiatric disorders. As part of his research, he created an image of the mouse brain that captured the social reward circuit under the microscope. 

What does this image show?

We study how animals find social interactions rewarding, and we try to identify neural circuits that mediate the social reward process. For this study, we focused on the medial amygdala, which detects social sensory cues. In the image, the blue is a counter stain for nuclei so that we can gain an idea of the overall brain structure, and the green depicts axonal projections from the GABAergic neurons of the medial amygdala to a hypothalamic area called the medial preoptic nucleus. We discovered that this pathway mediates the effects of social rewards. 

How did you create the image?

We created a task where an animal made one of two choices. One option gave access to another animal to interact with for a few seconds, and the other option did nothing. Over days, the animal learned the choice that rewarded it with social interaction and developed a strong preference for that choice. 

To study neural circuits in the brain that regulate social reward behavior, we used a modified experimental setup by replacing social interaction with stimulation of the social reward circuit shown in the image. Animals developed a preference for the choice that stimulated the same axons activated during social interaction, indicating that stimulating these axons was particularly rewarding to the animals. We visualized this social reward circuit under a microscope, and that is what we see in this image. 

What is the next unanswered question you plan to address?

There are many questions. For example, how does this social reward circuit change in disease conditions such as autism spectrum disorder? Patients with autism have reduced or impaired social behavior. Could that be due to reduced social motivation and social reward? I believe that we can make unique contributions to this area by studying these circuits and using this experimental setup. 

What implications does this study have for future research?

Normally, humans find a lot of things rewarding, like our favorite foods. The reason we like those foods is that they give us pleasant experiences. How is that different from the rewarding experience of social interaction? In this study, we identified unique brain areas dedicated to social interaction, and we found that this circuit activated by social interaction is not relevant to food rewards. I think that has profound implications for the study of motivation. Depression can decrease social reward and motivation, while addiction can hijack normal reward and motivation circuitry in the brain. This study improves understanding of what brain areas should be studied to understand altered social motivation. 

This interview has been condensed and edited for clarity

About the Author

  • Angela Zhang, PhD Headshot

    Angela is an assistant editor at DDN. She obtained her PhD in Neuroscience from McGill University in 2021 where she researched computational patterns of the brain with big data functional MRI approaches. Throughout her science career she has worked as a freelance designer and scientific illustrator, bringing together her passions in science and art. When not editing, you can find Angela attending concerts and exploring new restaurants in Montreal.

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