Differential activation of chemically identified neurons in the caudal nucleus of the solitary tract in non-entrained rats after intake of satiating vs. non-satiating meals

Abstract

Satiety signals arising from the gastrointestinal (GI) tract and related digestive organs during food ingestion and digestion are conveyed by vagal sensory afferents to the hindbrain nucleus of the solitary tract (NST). Two intermingled but chemically distinct NST neuronal populations have been implicated in meal size control: noradrenergic (NA) neurons that comprise the A2 cell group, and glucagon-like peptide-1 (GLP-1)-positive neurons. Previous results indicate that A2 neurons are activated in a meal size-dependent manner in rats that have been acclimated/entrained to a feeding schedule in order to increase meal size, whereas feeding under the same conditions does not activate GLP-1 neurons. The present study was designed to test the hypothesis that both A2 and GLP-1 neuronal populations are recruited in non-entrained rats after voluntary first-time intake of an unrestricted, satiating volume of liquid Ensure. DBH-positive A2 neurons within the caudal visceral NST were progressively recruited to express cFos in rats that consumed progressively larger volumes of Ensure. Among these DBH-positive neurons, the prolactin-releasing peptide (PrRP)-positive subset was more sensitive to feeding-induced activation than the PrRP-negative subset. Notably, significant activation of GLP-1-positive neurons occurred only in rats that consumed the largest volumes of Ensure, corresponding to nearly 5% of their BW. We interpret these results as evidence that progressive recruitment of NA neurons within the caudal NST, especially the most caudally-situated PrRP-positive subset, effectively "tracks" the magnitude of GI satiety signals and other meal-related sensory feedback. Conversely, GLP-1 neurons may only be recruited in response to the homeostatic challenge of consuming a very large, unanticipated meal.

Keywords: A2 cell group; Glucagon-like peptide-1; Prolactin-releasing peptide; Re-feeding; Satiety; cFos.

Fig. 1

GLP-1-positive (B) and DBH+PrRP-positive (C) neurons within the caudal NST (region indicated by red arrow in panel A) are activated to express cFos in representative rats that consumed an unrestricted (B) or 30% restricted (C) Ensure meal after food deprivation. White arrows point out some of the double-labeled neurons visible within each photomicrograph, in which nuclear cFos immunolabeling is co-localized with cytoplasmic GLP-1 or DBH+PrRP immunolabeling. Brain schematic image in panel A adapted from (45). Scale bars in B and C = 50 μm.

Fig. 2

Percentage of GLP-1-immunopositive NST neurons that express cFos immunoreactivity in response to meals of increasing size (see Table 1). Different letters indicate statistically significant differences in cFos activation between feeding condition groups (p < .05).

Fig. 3

Percentage of DBH-immunopositive neurons, either PrRP-positive or PrRP-negative, that express cFos immunoreactivity in response to meals of increasing size (see Table 1). Within each phenotypic subgroup of DBH-positive neurons, different letters indicate significant differences in cFos activation between feeding condition groups (p < .05).

Fig. 4

Relationship between meal size and percentage of GLP-1-positive neurons activated to express cFos in rats that consumed unrestricted, satiating volumes of Ensure (black dots). Data points representing non-fed controls (n=7) are added for comparison (open squares). Each symbol represents one animal. Best-fit line and correlation statistics refer only to rats in the unrestricted feeding group.

Fig. 5

Relationship between meal size and percentage of PrRP-positive neurons expressing cFos in rats that consumed unrestricted, satiating volumes of Ensure (black dots). Data points representing non-fed controls (n=7) are added for comparison (open squares). Each symbol represents one animal. Best-fit line and correlation statistics refer only to rats in the unrestricted feeding group.