Statistical modeling implicates neuroanatomical circuit mediating stress relief by ‘comfort’ food

Abstract

A history of eating highly-palatable foods reduces physiological and emotional responses to stress. For instance, we have previously shown that limited sucrose intake (4 ml of 30% sucrose twice daily for 14 days) reduces hypothalamic-pituitary-adrenocortical (HPA) axis responses to stress. However, the neural mechanisms underlying stress relief by such ‘comfort’ foods are unclear, and could reveal an endogenous brain pathway for stress mitigation. As such, the present work assessed the expression of several proteins related to neuronal activation and/or plasticity in multiple stress- and reward-regulatory brain regions of rats after limited sucrose (vs. water control) intake. These data were then subjected to a series of statistical analyses, including Bayesian modeling, to identify the most likely neurocircuit mediating stress relief by sucrose. The analyses suggest that sucrose reduces HPA activation by dampening an excitatory basolateral amygdala - medial amygdala circuit, while also potentiating an inhibitory bed nucleus of the stria terminalis principle subdivision-mediated circuit, resulting in reduced HPA activation after stress. Collectively, the results support the hypothesis that sucrose limits stress responses via plastic changes to the structure and function of stress-regulatory neural circuits. The work also illustrates that advanced statistical methods are useful approaches to identify potentially novel and important underlying relationships in biological data sets.

Sucrose-induced plasticity in the basolateral amygdala in a ‘comfort’ feeding paradigm

“…In both strains, sucrose-fed rats had a reduced integrated plasma corticosterone response relative to water controls ( Long-Evans : t 22 = 1.94, p =0.032; Wistar : t 22 = 2.19, p = 0.019; Figure 1g,h). These results mirror those observed previously for this paradigm (Ulrich-Lai et al 2007; Ulrich-Lai et al 2010; Christiansen et al 2011; Ulrich-Lai et al 2011; Ulrich-Lai et al 2015; Egan and Ulrich-Lai 2015) and indicate that the LSI paradigm effectively reduces HPA axis responses to acute stress in rats of both ages and strains.…”

“…Output from BLA principal neurons is primarily thought to increase stress responses (Coover et al 1973; Feldman et al 1983; Szafarczyk et al 1986; Goldstein et al 1996; Bhatnagar et al 2004), so we postulated that sucrose acts by reducing stress-excitatory BLA output. Moreover, analyses of BLA mRNA and protein expression suggest that this reduced stress-excitatory output may be mediated by sucrose-induced neural plasticity in the BLA (Ulrich-Lai et al 2010; Christiansen et al 2011; Ulrich-Lai et al 2015; Egan and Ulrich-Lai 2015). Therefore, we measured indices of structural and functional plasticity in the BLA following LSI.…”

“…Experiment 1 was performed at the University of Cincinnati and consisted of the anatomical assessments of BLA appositions; the LSI paradigm was administered to 8–10 week old, male Long-Evans rats as described in previous studies with the LSI paradigm (Ulrich-Lai et al 2007; Ulrich-Lai et al 2010; Christiansen et al 2011; Ulrich-Lai et al 2011; Ulrich-Lai et al 2015; Egan and Ulrich-Lai 2015). A follow-up anatomical assessment was performed using brain tissue sections from (Egan and Ulrich-Lai 2015) to assess the impact of repeated sucrose consumption on the expression of pCREB-immunolabeling within PV-positive interneurons.…”

Self-medication with sucrose

“…Sucrose intake activates several reward-regulatory brain sites, and over the long-term induces synaptic plasticity in these regions [58,69-71]. LSI also attenuates stress-induced cFos mRNA induction in the basolateral amygdala (BLA) – a brain region that is important for both reward and stress regulation [10].…”

“…Finally, in order to more broadly identify the neuronal network by which LSI blunts HPA axis activity, statistical modeling was performed on a large dataset that measured multiple synaptic plasticity proteins in several reward- and stress-regulatory brain sites following LSI. The results implicated two concurrent neuronal pathways underlying the stress relief – reduced activity of a stress-excitatory pathway between the BLA and medial amygdala, as well as potentiation of a stress-inhibitory pathway from the bed nucleus of the stria terminalis, which together result in less stress-excitatory drive to downstream effector sites like the PVN [69]. Future work can now empirically test these predictions to uncover the neuronal mechanisms by which the hedonic and rewarding properties of sucrose contribute to its stress-relieving effects.…”