Major Theme
Our ultimate goal is to investigate the mechanisms by which stress influences brain plasticity and resilience. The stress response is key to organism survival: It is highly conserved across vertebrate species and it allows organisms to respond to environmental change. However, a stress response that persists or is repeatedly activated can have substantial negative consequences on brain plasticity and resilience. A reduction in brain plasticity is thought to contribute to many psychological conditions, such as depression, anxiety disorders, post-traumatic stress disorder (PTSD) and Alzehimer's disease. Chronic stress may even accelerate aging processes, which can be exacerbated by poor diet and other contributing variables. Consequently, studying conditions that attenuate or accentuate brain plasticity are essential to understanding mechanisms of adaptation and many neurological disorders.

Current Research Questions

1. What is the functional significance of neuronal restructuring produced by chronic stress?

Chronic stress alters the brain in many ways, with limbic structures being particularly susceptible to modifications. One of these changes include the remodeling of dendritic arbors within the hippocampus, amygdala and prefrontal cortex. Historically, our studies have shown that chronic stress impairs the function of the hippocampus (spatial ability) and prefrontal cortex (recall of fear extinction), and potentiates the function of the amygdala (acquisition of fear conditioning). However, we have observed exceptions, such as when stress steroids are modified during the training and testing paradigm (Wright et al., 2006) or when chronic stress is studied in females (see question #3). We are currently investigating the functional significance using a systems-level approach to investigate the how other neural substrates may be involved in spatial abilities following chronic stress.

Please see review papers: Conrad, C.D. (2006). What is the functional significance of chronic stress-induced CA3 dendritic retraction within the hippocampus? Behav. Cogn. Neurosci. Rev., 5, 41-60; Conrad, C.D. (2008). Chronic stress-induced hippocampal vulnerability: The Glucocorticoid Vulnerability Hypothesis. Rev. Neurosci., 19(6), 395-412; Conrad, C.D. (2010). A critical review of chronic stress effects on spatial learning and memory. Prog. Neuro-Psychopharm. Biol. Psychiat., 34, 742-755.

2. What factors contribute to one's susceptibility and resilience to chronic stress?

We are currently investigating signaling pathways that can facilitate or hinder the detrimental effects of chronic stress on spatial learning and memory. In males, chronic stress impairs hippocampal-dependent spatial ability, which can recover following the termination of chronic stress. Recently, we reported that chronically stressed rats given the opportunity to recover may even demonstrate facilitiated spatial ability compared to nonstressed controls (see Hoffman et al., 2011, Eur. J. Neurosci., 24, p. 1023). We are currently investigating the the mechanisms that facilitate this ability to recover following chronic stressors, including environmental conditions, such as enriched environments (Wright and Conrad, 2008, Brain Res., 187, p.41).

Please see book Conrad, C.D. (2011). The Handbook of Stress: Neuropsychological Effects on the Brain, Wiley-Blackwell Publishers; and see review paper: Conrad, C.D. and Bimonte-Nelson, H.A. (2010). Impact of the hypothalamic-pituitary-adrenal / gonadal axes on the trajectory of age-related cognitive decline. In Neuroendocrinology-pathological Situations and Diseases, Martini, L. (Ed.) Elsevier Press.

3. How does gender influence the effects of chronic stress on brain morphology and function?

The effects of chronic stress on hippocampal dendritric complexity and function differ between the sexes. In our paradigm using daily restraint (see McLaughlin et al., 2007, Brain Res., 1161, p. 56), chronic stress produces CA3 dendritic retraction and impaired spatial ability in males, but not in females. For females, ovarian hormones contribute to some of these differences (McLaughlin et al., 2005, 2010; Conrad et al., 2012), by protecting against stress-induced CA3 dendritic retraction (Mclaughlin et al., 2010, Conrad et al., 2012), but chronically stressed females still show functional spatial ability despite CA3 dendritic restraction (McLaughlin et al., 2010; Conrad et al., 2012). Current work teases apart contributing variables to these sex differences (Baran et al., 2010; Hoffman et al., 2010; Huynh et al., 2011). 

Please see review papers: McLaughlin, K.J., Baran, S.E. and Conrad, C.D. (2009).Chronic stress- and sex-specific neuromorphological and functional changes in limbic structures. Mol. Neurobiol., 40, 166-182, and also, Conrad, C.D. and Bimonte-Nelson, H.A. (2010). Impact of the hypothalamic-pituitary-adrenal / gonadal axes on the trajectory of age-related cognitive decline. In Neuroendocrinology-pathological Situations and Diseases, Martini, L. (Ed.) Elsevier Press.