Examining the role of cell adhesion molecules in emotional reactivity using the bred high-responder/bred low-responder model

Stefanov AV, Hilde KH, Birt I, Hagenauer MH, Hebda-Bauer EK, Clinton SM, Aydin C, Blandino P, Stead J, Thompson RC, Watson SJ, Akil H
Society for Neuroscience. 2017.


In the United States, over a quarter of adults eighteen years or older are diagnosed with a psychiatric disorder over a twelve-month period, where the most common classes reported are anxiety and mood disorders. Developing treatments for individuals susceptible to depression and anxiety requires a better understanding of the underlying neural and molecular mechanisms.
Cell adhesion molecules (CAMs) are essential for the organization and communication of neighboring cells in the nervous system of a developing organism, as they orchestrate growing neurons into neural networks and help develop and maintain the synapses between them. The structures, molecular pathways, and interactions of various CAMs have been extensively studied in neural systems, and individual CAMs have been implicated in psychiatric disease. However, we know very little about the role of this broad class of molecules in the development and fine-tuning of emotional brain circuitry.
To assess how CAMs affect the trajectory of neural circuits implicated in vulnerability to depression, we use a selectively-bred rat model of emotional reactivity: the bred high-responders (bHRs) and the bred low-responders (bLRs). bHRs exhibit higher locomotor activity, show greater sensation-seeking and impulsivity, have a propensity toward addiction, and demonstrate a greater tendency for social interaction. bLRs display lower locomotor activity, exhibit greater anxiety and depression behaviors, are more reactive to stress, and are less socially interactive. In this study, we have examined the developmental pattern of CAM gene expression in the hippocampus, an area critical for learning, memory, stress responsiveness, and the regulation of emotionality.
We will outline the phenotypic and age differences in the expression of various CAMs in the hippocampus of neonate, adolescent, and adult bHRs and bLRs. We will show that CAMs can be expressed strongly at certain time points in development while exhibiting low expression at other times. We will describe the phenotypic specificity of these developmental trajectories. Our findings suggest that emotional reactivity, which contributes to susceptibility to mood disorders, may depend in part on the temporally regulated expression of specific CAMs during development.