Differences in the morphology of microglia cells in the hippocampus of selectively bred high- and low-responder rats: Implications for emotional temperament

Maras PM, Hebda-Bauer EK, Akil H, Watson SJ
Society for Neuroscience. 2019.


Mood regulation is a complex process, influenced by both genetic and environmental factors, and reflecting underlying differences in emotional vulnerability. Individual differences in affective temperament clearly play an important role in mood disorders, yet their neural mechanisms remain unclear. Our laboratory uses a selective breeding technique, which has generated rats with contrasting emotional temperaments, to study the neurobiology of mood disorders. Specifically, rats bred for high locomotor responses when placed in a novel environment (bHRs) exhibit low anxiety and are resilient to depression, whereas rats bred for low locomotion in a novel environment (bLRs) are highly anxious and vulnerable to depression. Among the possible factors underlying the bHR/bLR phenotype, recent mRNA expression studies suggest that bLRs have elevated expression of key microglia-specific genes within their hippocampus compared to bHRs. Although intriguing, and consistent with a role for microglia in mood regulation, these expression data do not reveal the anatomical details of the microglia population, or distinguish between variations in the total number of microglia vs. their state of activation. The goal of the current set of experiments was therefore to fully characterize the number and morphology of microglia cells within the hippocampus of bHRs and bLRs under basal (non-stimulated) conditions. To this end, coronal brain sections from adult male bHRs and bLRs were labeled for the microglia marker Iba-1 using immunohistochemistry. Unbiased stereological procedures were used to estimate the total number of Iba-1-positive cells within the dorsal hippocampus. Further morphological analysis was accomplished using Neurolucida software to create detailed 3-D reconstructions of a subset of microglia cells. Although bHRs and bLRs did not differ in their total numbers of microglia cells, reconstruction analysis revealed interesting differences in the morphology of microglia, particularly within the resting state. These results provide a comprehensive comparison of the microglia population between rats bred for vulnerable or resilient phenotypes, and suggest that variability in microglia morphology may have functional consequences for emotional regulation and the development of mood disorders.