Interoceptive modulation of neuroendocrine, emotional, and hypophagic responses to stress

Abstract

Periods of caloric deficit substantially attenuate many centrally mediated responses to acute stress, including neural drive to the hypothalamic-pituitary-adrenal (HPA) axis, anxiety-like behavior, and stress-induced suppression of food intake (i.e., stress hypophagia). It is posited that this stress response plasticity supports food foraging and promotes intake during periods of negative energy balance, even in the face of other internal or external threats, thereby increasing the likelihood that energy stores are repleted. The mechanisms by which caloric deficit alters central stress responses, however, remain unclear. The caudal brainstem contains two distinct populations of stress-recruited neurons [i.e., noradrenergic neurons of the A2 cell group that co-express prolactin-releasing peptide (PrRP+ A2 neurons), and glucagon-like peptide 1 (GLP-1) neurons] that also are responsive to interoceptive feedback about feeding and metabolic status. A2/PrRP and GLP-1 neurons have been implicated anatomically and functionally in the central control of the HPA axis, anxiety-like behavior, and stress hypophagia. The current review summarizes a growing body of evidence that caloric deficits attenuate physiological and behavioral responses to acute stress as a consequence of reduced recruitment of PrRP+ A2 and hindbrain GLP-1 neurons, accompanied by reduced signaling to their brainstem, hypothalamic, and limbic forebrain targets.

A hippocampus to prefrontal cortex neural pathway inhibits food motivation through glucagon-like peptide-1 signaling

“…Both vHP and mPFC neural processing, as well as CNS GLP-1R signaling are capable of regulating both food and non-food motivated behaviors, particularly anxiety and stress 3 – 7 , 77 – 79 . However, our results indicate that vHP GLP-1R activation does not impact anxiety-like behaviors in the Zero maze task ( Supplemental Figure S1 ), an established rodent assay for anxiety-like behaviors.…”

GLP‐1 neurons form a local synaptic circuit within the rodent nucleus of the solitary tract

“…Hindbrain GLP‐1 neurons and PrRP+ A2 neurons are robustly activated in rats after exposure to visceral or cognitive stressors, and published evidence supports the view that both neural populations contribute to the central control of stress responsiveness and motivated behavior via widespread axonal projections that reach multiple CNS regions implicated in these processes (Banihashemi & Rinaman, ; Bechtold & Luckman, ; Ellacott et al, ; Gu et al, ; Holt & Trapp, ; Kreisler, Davis, & Rinaman, ; Larsen et al, ; Lawrence et al, ; Lawrence, Ellacott, & Luckman, ; Lawrence, Liu, Stock, & Luckman, ; Llewellyn‐Smith et al, ; Maniscalco et al, , ; Maniscalco & Rinaman, ; Myers & Rinaman, ; Rinaman, , , 2010; Trapp & Cork, ; Zheng & Rinaman, ) . GLP‐1R expression by PrRP+ neurons could contribute to local modulatory effects on Ca 2+ signaling within the local somatodendritic compartment of PrRP neurons, and/or distal axo‐axonic interactions that affect release of norepinephrine and PrRP within CNS target regions that receive axonal input from both cNTS neural populations (Maniscalco & Rinaman, ; Maniscalco et al, ; Rinaman, 2010). Interestingly, restraint stress activates cFos expression by both GLP‐1+ and PrRP+ neurons in rats, identifying both neural populations as “stress‐sensitive” (Maniscalco et al, ).…”

From Stress to Anhedonia: Molecular Processes through Functional Circuits

“…GLP-1-producing neurons originate almost exclusively in the caudal nucleus of the solitary tract (cNST) in the brainstem [78]. These projections play key roles in decreasing food intake both during satiety [79,80] and following stress [81]. GLP-1 signaling appears to decrease the rewarding value of food [82] through direct projections to NAc and VTA [83] (Figure 1).…”