Postnatal development of the hippocampus in the Rhesus macaque (Macaca mulatta): a longitudinal magnetic resonance imaging study

Abstract

Nonhuman primates are widely used models to investigate the neural substrates of human behavior, including the development of higher cognitive and affective function. Due to their neuroanatomical and behavioral homologies with humans, the rhesus macaque monkey (Macaca mulatta) provides an excellent animal model in which to characterize the maturation of brain structures from birth through adulthood and into senescence. To evaluate hippocampal development in rhesus macaques, structural magnetic resonance imaging scans were obtained longitudinally at 9 time points between 1 week and 260 weeks (5 years) of age on 24 rhesus macaque monkeys (12 males, 12 females). In our sample, the hippocampus reaches 50% of its adult volume by 13 weeks of age and reaches an adult volume by 52 weeks in both males and females. The hippocampus appears to be slightly larger at 3 years than at 5 years of age. Male rhesus macaques have larger hippocampi than females from 8 weeks onward by approximately 5%. Interestingly, there was increased variability in hemispheric asymmetry for hippocampus volumes at younger ages than at later ages. These data provide a comprehensive evaluation of the longitudinal development of male and female rhesus macaque hippocampus across development from 1 week to 5 years of age.

Keywords: Rhesus macaque; hippocampus; longitudinal development; magnetic resonance imaging; primate model.

Figure 1. Sample hippocampal tracings from a single male rhesus macaque

Shown are scans at 1 week, 4 week, 26 weeks, 39 weeks, and 260 weeks of age. Note the difference in white matter at the different ages. All scans are shown at the same scale for direct visual comparison. Note the general shape of the traced hippocampus and size relative to the rest of brain at different ages. Scale bar = 1 cm.

Figure 2. Three-Dimensional Renderings of hippocampus for a single male rhesus macaque across all ages

All renderings are shown at the same orientation and relative scale for direct visual comparison. The renderings for the male rhesus macaque are from the same subject shown in Figure 1. Scale bar = 1 cm.

Figure 3. Longitudinal growth curves for male and female rhesus macaque hippocampus

All data points are shown. The X axis shows the age of the primate at scanning. Note the nonlinear growth curves and similarity among male and female rhesus macaque primates.

Figure 4. Longitudinal growth curves for male and female rhesus macaque hippocampus

All data points are shown. The X axis shows the age plotted on a log₁₀ time scale to more clearly show volume differences at different ages.

Figure 5. Hemispheric asymmetry for all rhesus macaque hippocampus

The Y axis compares the volume of the right hippocampus to the volume of the let hippocampus in each individual primate. A larger left hippocampus is indicated by a data point above the baseline. The X axis shows the age of the primates.