By Marilynn Larkin

The hippocampus contains neurons that specifically encode memories of sugar and fat, influencing food intake and body weight in mice, and possibly in humans, new research suggested.

“The hippocampus has emerged as a critical player in the control of food intake, beyond its well-known role in memory,” according to Guillaume de Lartigue, PhD, associate member, Monell Chemical Senses Center in Philadelphia, and colleagues. “While previous studies have primarily associated the [hippocampus] with food intake inhibition, recent research suggests a role in appetitive processes.”

In a series of experiments, the researchers identified distinct populations of neurons in the dorsal hippocampus of the mouse brain that respond specifically to either fats or sugars. Fat-responsive neurons enhanced the preference and motivation for fat intake, whereas sugar-responsive neurons encoded spatial memory for sugar location.

Stimulating either of these cell populations increased food intake. In contrast, silencing those neurons seemed to impair the animals’ ability to recall sugar-related memories, thereby reducing sugar consumption and preventing weight gain, even when animals were exposed to diets that contributed to excessive weight gain.

Reactivating those neurons enhanced memory for food, increasing consumption and suggesting how food memories influence dietary behavior.

“Recent research is bringing us closer to understanding how these mechanisms might operate in humans,” said de Lartigue. “While these advancements are promising, direct evidence linking gut-derived nutrient signals to specific hippocampal circuits in humans is still lacking. The development of tools for real-time monitoring of gut-brain interactions, coupled with advanced neuroimaging and transcriptomic studies, will help bridge this gap.”

With these tools, he added, “we are optimistic that we could validate these circuits and their contributions to eating behavior in humans within the next 5-10 years.”

Potential Preventive Strategies

The study “offers strong evidence that hippocampal neurons, which encode memories related to food, play a crucial role in regulating eating behavior,” de Lartigue noted. Removing these neurons can reduce food intake, even when hunger or cravings would normally drive eating. “This suggests that these neurons can override signals that motivate eating, regardless of whether the trigger is physiological need or hedonic cravings,” he said.

If similar cell populations are found in humans, he said, several practical interventions could be employed:

Neuromodulation: “We found that nutrients in the gut are signaled to the hippocampus via the vagus nerve, so techniques like vagal nerve stimulation could be a viable strategy to activate the hippocampal neurons involved in feeding,” de Lartigue said. More targeted modes of neuromodulation, such as transcranial magnetic stimulation or focused ultrasound, might selectively influence the activity of these neurons.

Pharmacological interventions: “Drugs could be designed to target the specific receptors or signaling pathways expressed by these neurons, allowing precise modulation of their activity and ability to influence food-related episodic memory,” he suggested.

Dietary interventions: Controlled exposure to specific nutrients might help reshape food preferences and reduce the impact of food cues on behavior.

The overall goal would be to reduce the activity of these neurons to diminish their impact, de Lartigue said. “Using drugs to ‘turn down the volume’ of these neurons could reduce the influence of environmental cues that trigger food-related memories. This, in turn, might weaken the impulse to eat in response to these cues,” he added.

In a related editorial, Pierre Trifilieff and Guillaume Ferreira of the University of Bordeaux, France, wrote that the study shows that the presence of sugar-responsive and fat-responsive neurons in the dorsal hippocampus and the role they play make this region of the brain a key player in food behavior in mice.

“These findings advance our understanding of body-brain interaction and provide a new mechanism by which nutrient ingestion is encoded to drive behavior. They will pave the way for the development of novel strategies, such as vagal nerve stimulation, to treat or prevent eating disorders (and associated cognitive dysfunctions) and to counteract the obesogenic environment.”