Neuro-immune interactions across development: A look at glutamate in the prefrontal cortex

- The immune system influences normal synaptic communication and development.
- The quad-partite glutamatergic synapse is a juncture for neuro-immune communication.
- Prolonged neuro-immune development parallels prolonged cognitive development.
- Shifts in neuro-immune dynamics influence a variety of developmental disorders.

Although the primary role for the immune system is to respond to pathogens, more recently, the immune system has been demonstrated to have a critical role in signaling developmental events. Of particular interest for this review is how immunocompetent microglia and astrocytes interact with glutamatergic systems to influence the development of neural circuits in the prefrontal cortex (PFC). Microglia are the resident macrophages of the brain, and astrocytes mediate both glutamatergic uptake and coordinate with microglia to respond to the general excitatory state of the brain. Cross-talk between microglia, astrocytes, and glutamatergic neurons forms a quad-partite synapse, and this review argues that interactions within this synapse have critical implications for the maturation of PFC-dependent cognitive function. Similarly, understanding developmental shifts in immune signaling may help elucidate variations in sensitivities to developmental disruptions.