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Microglia Morphology in the Developing Primate Amygdala and Effects of Early Life Stress
Dennisha P King1, Miral Abdalaziz1, Ania K Majewska1
1Department of Neuroscience, University of Rochester Medical Center, Rochester, New York 14642.
Abstract:
A unique pool of immature glutamatergic neurons in the primate amygdala, known as the paralaminar nucleus (PL), are maturing between infancy and adolescence. The PL is a potential substrate for the steep growth curve of amygdala volume during this developmental period. A microglial component is also embedded among the PL neurons and likely supports local neuronal maturation and emerging synaptogenesis. Microglia may alter neuronal growth following environmental perturbations such as stress. Using multiple measures in rhesus macaques, we found that microglia in the infant primate PL had relatively large somas and a small arbor size. In contrast, microglia in the adolescent PL had a smaller soma and a larger dendritic arbor. We then examined microglial morphology in the PL after a novel maternal separation protocol, to examine the effects of early life stress. After maternal separation, the microglia had increased soma size, arbor size, and complexity. Surprisingly, strong effects were seen not only in the infant PL, but also in the adolescent PL from subjects who had experienced the separation many years earlier. We conclude that under normal maternal-rearing conditions, PL microglia morphology tracks PL neuronal growth, progressing to a more "mature" phenotype by adolescence. Maternal separation has long-lasting effects on microglia, altering their normal developmental trajectory, and resulting in a "hyper-ramified" phenotype that persists for years. We speculate that these changes have consequences for neuronal development in young primates.
Insights
Early life stress, like maternal separation, permanently alters brain microglia in infant and adolescent primates. These changes impact neuronal development and persist long-term, affecting brain maturation.
Area of Science:
- Neuroscience
- Developmental Biology
- Primate Research
Background:
- The primate amygdala, specifically the paralaminar nucleus (PL), undergoes significant growth and neuronal maturation from infancy to adolescence.
- Microglia, immune cells within the brain, are present in the PL and are thought to support neuronal development and synapse formation.
- Environmental factors, such as stress, may influence microglial function and subsequent neuronal maturation.
Purpose of the Study:
- To investigate the developmental trajectory of microglia within the primate PL from infancy to adolescence.
- To examine the impact of early life stress (maternal separation) on microglial morphology in the PL.
- To determine the long-lasting effects of early life stress on microglial development and neuronal maturation.
Main Methods:
- Utilized rhesus macaques for the study.
- Employed multiple measures to assess microglial morphology (soma size, arbor size, complexity) in the PL.
- Implemented a maternal separation protocol to induce early life stress.
Main Results:
- Infant PL microglia exhibited large somas and small arbors, while adolescent PL microglia showed smaller somas and larger arbors, indicating developmental maturation.
- Maternal separation led to increased soma size, arbor size, and complexity in PL microglia.
- These microglial alterations persisted even in adolescent subjects who experienced maternal separation years earlier.
Conclusions:
- Under typical conditions, PL microglial morphology matures in parallel with PL neuronal development.
- Early life stress, specifically maternal separation, disrupts the normal developmental trajectory of PL microglia, inducing a persistent "hyper-ramified" phenotype.
- These long-lasting microglial changes following stress may have significant consequences for primate brain development.
