Postmeal Optogenetic Inhibition of Dorsal or Ventral Hippocampal Pyramidal Neurons Increases Future Intake

Abstract

Memory of a recently eaten meal can serve as a powerful mechanism for controlling future eating behavior because it provides a record of intake that likely outlasts most physiological signals generated by the meal. In support, impairing the encoding of a meal in humans increases the amount ingested at the next eating episode. However, the brain regions that mediate the inhibitory effects of memory on future intake are unknown. In the present study, we tested the hypothesis that dorsal hippocampal (dHC) and ventral hippocampal (vHC) glutamatergic pyramidal neurons play a critical role in the inhibition of energy intake during the postprandial period by optogenetically inhibiting these neurons at specific times relative to a meal. Male Sprague Dawley rats were given viral vectors containing CaMKIIα-eArchT3.0-eYFP or CaMKIIα-GFP and fiber optic probes into dHC of one hemisphere and vHC of the other. Compared to intake on a day in which illumination was not given, inhibition of dHC or vHC glutamatergic neurons after the end of a chow, sucrose, or saccharin meal accelerated the onset of the next meal and increased the amount consumed during that next meal when the neurons were no longer inhibited. Inhibition given during a meal did not affect the amount consumed during that meal or the next one but did hasten meal initiation. These data show that dHC and vHC glutamatergic neuronal activity during the postprandial period is critical for limiting subsequent ingestion and suggest that these neurons inhibit future intake by consolidating the memory of the preceding meal.

Inhibition of the Ventral Hippocampus Increases Alcohol Drinking

“…Some reports indicate the involvement of the ventral hippocampus in models of feeding behavior using high concentrations of sucrose. Data from these experiments show that inhibition of ventral hippocampus function after concluding a meal increases feeding at the next meal (Hannapel et al 2019;Hannapel et al 2017), a finding broadly consistent with the data presented in this report. Thus, more work needs to be done to determine the role of the ventral hippocampus on consummatory behavior.…”

Hippocampal-dependent appetitive control is impaired by experimental exposure to a Western-style diet

“…[3,12,13]). We also noted that inhibitory hippocampal modulation of appetite in animals could occur independent of state [24], perhaps paralleling memory-based inhibition effects in people [11]. Returning to the accounts outlined in the Introduction, the incentive salience model was suggested to occur via internal state acting to dampen brain reward circuit activity.…”

“…Irrespective of which of these accounts of modulation might be correct, there are grounds for thinking that the hippocampus is involved in using interoceptive state to regulate appetite [11,23]-although noting that inhibitory effects in animals can be obtained seemingly independent of interoceptive state [24]. The hippocampus has an established experimental and theoretical history of involvement in inhibitory processing (e.g.…”

Ghrelin signaling regulates feeding behavior, metabolism, and memory through the vagus nerve

“…It is possible that the observed impairments in episodic memory are functionally related to the increased spontaneous meal frequency following VANspecific GHSR knockdown. Lesioning or inhibition of hippocampal neurons reduces the intermeal interval in rodent models, in addition to increasing intake at the next meal [31][32][33][34]. In humans, interfering with meal-related episodic memory (by decreasing perceived food intake while controlling for actual food intake) increases subjects' self-reported hunger rating during the intermeal interval [35], while a separate study showed that simply being asked to recall a previous meal decreases future intake at the subsequent meal [36].…”