Glia sculpt social behavior circuitry

Every brain is built, not born.

During development, the nervous system produces far more cells than it will ultimately keep. Some survive and become integrated into neural circuits. Others die or are systematically removed. These decisions determine the architecture of the brain itself and help shape how an animal perceives, responds to, and interacts with the world around it. Yet despite their importance, we still know remarkably little about the cellular mechanisms that govern these developmental choices.

One of the central questions in neuroscience is how this process unfolds. How does the developing brain construct the circuits that make social behavior possible? Why do individuals emerge from development with different social tendencies and social phenotypes? And how do disruptions during these early stages alter the trajectory of brain function months, years, or decades later?

For much of modern neuroscience, the answers to these questions have been sought primarily through neurons. Our work explores a different possibility: that some of the most important decisions in sculpting social behavior circuitry are made by the brain’s immune system.

We study microglia, the resident immune cells of the brain. Traditionally viewed as sentinels that protect the brain from injury and disease, microglia are now recognized as active participants in development. They interact directly with newly generated cells, influence who survives and who does not, and help shape the architecture of emerging neural circuits. In this sense, microglia are “editors” of the developing brain, continuously evaluating and refining the cellular landscape that underlies social behavior.

Our research asks how these developmental decisions are made.

What determines which newborn cells are eliminated and which are incorporated into lasting neural circuits? What signals tell microglia that one cell should be preserved while another should be removed? How do these choices influence the density, connectivity, and organization of social circuits? And perhaps most importantly, can a brief interaction between a microglial cell and its environment during a sensitive developmental window leave a lasting imprint on behavior months, or even years later?

Social behavior is among the most sophisticated achievements of the brain. It allows animals to form relationships, communicate, cooperate, compete, care for offspring, and navigate the complexities of social life. It is also remarkably fragile. Altered social behavior is a defining feature of numerous neurodevelopmental and neuropsychiatric disorders, including autism spectrum disorders, social anxiety, depression, addiction, and schizophrenia. Despite decades of research, we still know surprisingly little about the developmental mechanisms that construct the neural circuitry underlying these behaviors.

To understand how microglia shape social behavior circuitry, we follow biology across scales. Our work traces a continuous path from developmental cellular interactions, to neural circuit assembly, to behavior. By combining developmental birth-dating approaches, super resolution and 3D confocal imaging, molecular and pharmacological manipulations, cell type-specific viral tools, chemogenetics, and machine learning-driven behavioral analysis, we seek to establish causal links between events occurring in the developing brain with the behaviors that emerge later in life.

At its core, this work is driven by the simple idea: to understand the social brain, we first need to understand how it is built.

Ultimately, our goal is to understand how experience intersects with biology and becomes embedded in the structure of the developing brain. We seek to uncover the mechanisms that generate social circuits, explain why individuals differ from one another, and reveal how developmental pathways can be altered in conditions marked by social dysfunction.

And if microglia are essential to making the critical decisions that shape developing social circuits, then understanding their role may fundamentally change how we think about the origins of social behavior, individual behavioral diversity, and the developmental origins of disorders in which social behavior goes awry.