Disrupted maternal care alters neural-microglia interactions in the primate paralaminar (PL) nucleus of the amygdala

Prolonged postnatal maturation of the primate amygdala is thought to be driven, at least partially, by continued neural maturation within the paralaminar nucleus (PL). At birth, the PL is densely populated with post-mitotic glutamatergic neurons that gradually mature throughout postnatal life. This active process is likely supported by microglia, which promotes synaptic maturation. Our previous work showed that maternal separation alters microglia development across the infant to adolescent transition (n=19 females, 4 males). Here, in the same cohort, we examined whether morphologic microglial changes are associated with alterations in the numbers of pre-synaptic terminals (SYN1+ puncta), post-synaptic terminals (PSD95+ puncta), and putative excitatory contacts (SYN1-PSD95 colocalization), and whether these synaptic elements are engulfed by phagocytic microglia. In maternally reared macaques, SYN1+ puncta, PSD95+ puncta, and putative synaptic contacts decreased, while microglial (IBA1+) volume, CD68+ content, and engulfment of synaptic elements increased between infancy and adolescence. These findings suggest greater pruning of all synaptic elements by adolescence. Maternal separation altered this trajectory, resulting in increased phagocytic activity and engulfment of synaptic elements primarily during infancy. Maternal separation also resulted in a 50% reduction in mature PL neurons by adolescence, suggesting maturational failure, cell loss, or both by adolescence. These findings demonstrate that early life stress disrupts normative synaptic pruning and microglia-synapse interactions in the developing primate PL. Increased synaptic engulfment in infants with disrupted care is associated with premature, aberrant pruning and highlights a potential cellular mechanism through which early environmental insults could change PL neural development by adolescence.Significance Statement The paralaminar nucleus (PL) of the amygdala is an important substrate for the delayed post-natal development of the amygdala in human and nonhuman primates. Gradually maturing glutamatergic neurons in this region, and the microglia that support them, are exposed to life events that may shape their development. We recently found that maternal separation in infants produces aberrant hyper-ramified microglia in the PL beginning in infancy and persisting into adolescence. Examining neuron-microglial interactions in the same cohort, we now find increased phagocytic engulfment of synaptic elements by microglia after maternal separation in infancy only, with a reduction in PL mature neurons that is apparent by adolescence. Together, these data suggest a mechanism for altered PL maturation, instigated by disrupted maternal care.