Inhibiting ventral hippocampal NMDA receptors and Arc increases energy intake in male rats.

Research into the neural mechanisms that underlie higher-order cognitive control of eating behavior suggests that ventral hippocampal (vHC) neurons, which are critical for emotional memory, also inhibit energy intake. We showed previously that optogenetically inhibiting vHC glutamatergic neurons during the early postprandial period, when the memory of the meal would be undergoing consolidation, caused rats to eat their next meal sooner and to eat more during that next meal when the neurons were no longer inhibited. The present research determined whether manipulations known to interfere with synaptic plasticity and memory when given pretraining would increase energy intake when given prior to ingestion. Specifically, we tested the effects of blocking vHC glutamatergic N-methyl-D-aspartate receptors (NMDARs) and activity-regulated cytoskeleton-associated protein (Arc) on sucrose ingestion. The results showed that male rats consumed a larger sucrose meal on days when they were given vHC infusions of the NMDAR antagonist APV or Arc antisense oligodeoxynucleotides than on days when they were given control infusions. The rats did not accommodate for that increase by delaying the onset of their next sucrose meal (i.e., decreased satiety ratio) or by eating less during the next meal. These data suggest that vHC NMDARs and Arc limit meal size and inhibit meal initiation.

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

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.

Sucrose ingestion induces glutamate AMPA receptor phosphorylation in dorsal hippocampal neurons: Increased sucrose experience prevents this effect.

Evidence suggests that meal-related memory influences later eating behavior. Memory can serve as a powerful mechanism for controlling eating behavior because it provides a record of recent intake that likely outlasts most physiological signals generated by ingestion. Dorsal (dHC) and ventral hippocampal (vHC) neurons are critical for memory, and we demonstrated previously that they limit energy intake during the postprandial period. If dHC or vHC neurons control intake through a process that requires memory, then ingestion should increase events necessary for synaptic plasticity in dHC and vHC during the postprandial period. To test this, we determined whether ingesting a sucrose solution induced posttranslational events critical for hippocampal synaptic plasticity: phosphorylation of AMPAR GluA1 subunits at 1) serine 831 (pSer831) and 2) serine 845 (pSer845). We also examined whether increasing the amount of previous experience with the sucrose solution, which would be expected to decrease the mnemonic demand involved in an ingestion bout, would also attenuate sucrose-induced phosphorylation. Quantitative immunoblotting of dHC and vHC membrane fractions demonstrated that sucrose ingestion increased postprandial pSer831 in dHC but not vHC. Increased previous sucrose experience prevented sucrose-induced dHC pSer831. Sucrose ingestion did not affect pSer845 in either dHC or vHC. Thus, the present findings show that ingestion activates a postranslational event necessary for synaptic plasticity in an experience-dependent manner, which is consistent with the hypothesis that dHC neurons form a memory of a meal during the postprandial period.

Ventral hippocampal neurons inhibit postprandial energy intake.

Evidence suggests that the memory of a recently ingested meal limits subsequent intake. Given that ventral hippocampal (vHC) neurons are involved in memory and energy intake, the present experiment tested the hypothesis that vHC neurons contribute to the formation of a memory of a meal and inhibit energy intake during the postprandial period. We tested (1) whether pharmacological inactivation of vHC neurons during the period following a sucrose meal, when the memory of the meal would be undergoing consolidation, accelerates the onset of the next sucrose meal and increases intake and (2) whether sucrose intake increases vHC expression of the synaptic plasticity marker activity-regulated cytoskeletal-associated protein (Arc). Adult male Sprague-Dawley rats were trained to consume a 32% sucrose solution daily at the same time and location. On the experimental day, the rats were given intra-vHC infusions of the GABAA receptor agonist muscimol or vehicle after they finished their first sucrose meal. Compared to vehicle infusions, postmeal intra-vHC muscimol infusions decreased the latency to the next sucrose meal, increased the amount of sucrose consumed during that meal, increased the total number of sucrose meals and the total amount of sucrose ingested. In addition, rats that consumed sucrose had higher levels of Arc expression in both vHC CA1 and CA3 subfields than cage control rats. Collectively, these findings are the first to show that vHC neurons inhibit energy intake during the postprandial period and support the hypothesis that vHC neurons form a memory of a meal and inhibit subsequent intake. © 2016 Wiley Periodicals, Inc.