Remembering to eat: hippocampal regulation of meal onset

Abstract

A wide variety of species, including vertebrate and invertebrates, consume food in bouts (i.e., meals). Decades of research suggest that different mechanisms regulate meal initiation (when to start eating) versus meal termination (how much to eat in a meal, also known as satiety). There is a very limited understanding of the mechanisms that regulate meal onset and the duration of the postprandial intermeal interval (ppIMI). In the present review, we examine issues involved in measuring meal onset and some of the limited available evidence regarding how it is regulated. Then, we describe our recent work indicating that dorsal hippocampal neurons inhibit meal onset during the ppIMI and describe the processes that may be involved in this. We also synthesize recent evidence, including evidence from our laboratory, suggesting that overeating impairs hippocampal functioning and that impaired hippocampal functioning, in turn, contributes to the development and/or maintenance of diet-induced obesity. Finally, we identify critical questions and challenges for future research investigating neural controls of meal onset.

Keywords: energy intake; hippocampus; meal onset; memory; obesity.

Fig. 1.

Reversible inactivation of dorsal hippocampal neurons with muscimol (Mus) during the postprandial period decreases the duration of the postprandial intermeal interval (ppIMI; A), decreases the satiety ratio (duration of the ppIMI/size of the preceding meal) (B), and prevents the postprandial correlation (positive association between the size of a meal and the length of time before the next meal is initiated) (C). *P < 0.05 and ** P < 0.01 vs. vehicle (Veh) infusions. Adapted with permission from Ref. [Henderson, Y.O., Smith, G. P., and Parent, M. B., Hippocampus, Hippocampal neurons inhibit meal onset. 23: 100–107, 2013 (doi: 10.1002/hipo.22062)].

Fig. 2.

Reversible inactivation of dorsal hippocampal neurons with muscimol during the postprandial period increases the postinfusion meal size (A) and increases the duration of the postinfusion meal (B). *P < 0.05 vs. vehicle infusions. Adapted with permission from Ref. [Henderson, Y.O., Smith, G. P., and Parent, M. B., Hippocampus, Hippocampal neurons inhibit meal onset. 23: 100–107, 2013 (doi: 10.1002/hipo.22062)].

Fig. 3.

Rats that gain the most body mass during the first 5 days on a high-energy cafeteria style diet (HED-Obese) are impaired 8 wk later on a hippocampal-dependent memory test. Rats that gain the least amount of weight during the first 5 days (i.e., HED-Lean) do not develop memory deficits. On the memory test, HED-Obese rats had longer latencies to reach the platform location (A), spent less time in the target quadrant (B), and swam further away from the platform location (C) *P < 0.05 vs. standard chow controls; #P < 0.05 vs. HED-Lean; +P < 0.05 vs. standard chow controls; main effect P = 0.053. Adapted with permission from Ref. [Darling, J. N., Ross, A. P., Bartness, T. J., and Parent, M. B., Obesity (Silver Spring), Predicting the effects of a high-energy diet on fatty liver and hippocampal-dependent memory in male rats. 21: 910–917, 2013 (doi: 10.1002/oby.20167)].

Fig. 4.

The effects of high-energy diets on memory are modestly but significantly correlated with the effects of the diets on hepatic liver lipid concentrations (P < 0.05). Adapted with permission from Ref. [Darling, J. N., Ross, A. P., Bartness, T. J., and Parent, M. B., Obesity (Silver Spring), Predicting the effects of a high-energy diet on fatty liver and hippocampal-dependent memory in male rats. 21: 910–917, 2013 (doi: 10.1002/oby.20167)].

Fig. 5.

The memory-impairing effects of high-energy diets are associated with elevated liver lipids rather than elevated body mass. Rats fed a 60% fructose diet for 12 wk meet the human diagnostic criterion for nonalcoholic fatty liver disease (NAFLD). Liver sections stained with hematoxylin and oil red-O reveal that NAFLD rats have larger and more numerous lipid droplets than control rats (A), have higher hepatic lipid concentrations (B), but do not have increased body mass (C). NAFLD rats display impaired memory on the hippocampal-dependent spatial water maze task, including longer latencies to reach the location where the platform was previously located (D) and fewer visits to the previous platform location (E) (*P < 0.05 vs. Control). Adapted with permission from Ref. [Reprinted from Physiology and Behavior 106, Ross, A. P., Bruggeman, E. C., Kasumu, A. W., Mielke, J. G., and Parent, M. B., Non-alcoholic fatty liver disease impairs hippocampal-dependent memory in male rats, 133–141, 2012, with permission from Elsevier].

Fig. 6.

Diet-induced obesity may be caused, at least in part, by a vicious cycle involving altered hippocampal function. Ingestion of high-energy diets and numerous other stressors impair hippocampal-dependent memory, which in turn, decreases the ppIMI and increases meal frequency and meal size, thereby causing and/or perpetuating obesity and possibly exacerbating hippocampal damage.