Sweet orosensation induces Arc expression in dorsal hippocampal CA1 neurons in an Experience‐dependent manner

Abstract

There is limited knowledge regarding how the brain controls the timing of meals. Similarly, there is a large gap in our understanding of how top-down cognitive processes, such as memory influence energy intake. We hypothesize that dorsal hippocampal (dHC) neurons, which are critical for episodic memory, form a memory of a meal and inhibit meal onset during the postprandial period. In support, we showed previously that reversible inactivation of these neurons during the period following a sucrose meal accelerates the onset of the next meal. If dHC neurons form a memory of a meal, then consumption should induce synaptic plasticity in dHC neurons. To test this, we determined (1) whether a sucrose meal increases the expression of the synaptic plasticity marker activity-regulated cytoskeleton-associated protein (Arc) in dHC CA1 neurons, (2) whether previous experience with sucrose influences sucrose-induced Arc expression, and (3) whether the orosensory stimulation produced by the noncaloric sweetener saccharin is sufficient to induce Arc expression. Male Sprague-Dawley rats were trained to consume a sweetened solution at a scheduled time daily. On the experimental day, they were given a solution for 7 min, euthanized, and then fluorescence in situ hybridization procedures were used to measure meal-induced Arc mRNA. Compared to caged control rats, Arc expression was significantly higher in rats that consumed sucrose or saccharin. Interestingly, rats given additional experience with sucrose had less Arc expression than rats with less sucrose experience, even though both groups consumed similar amounts on the experimental day. Thus, this study is the first to suggest that orosensory stimulation produced by consuming a sweetened solution and possibly the hedonic value of that sweet stimulation induces synaptic plasticity in dHC CA1 neurons in an experience-dependent manner. Collectively, these findings are consistent with our hypothesis that dHC neurons form a memory of a meal.

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

“…The finding that increased sucrose experience prevented the ability of sucrose ingestion to elevate dHC pSer 831 is consistent with previous findings showing that the ability of a stimulus to activate pSer 831 depends on the history of synaptic activation [74], and with our previous results showing that increased sucrose experience attenuates sucrose-induced increases in dHC Arc expression [71]. Together, the Arc and pSer 831 results suggest that repeated consumption of the same meal may decrease the mnemonic demands associated with that meal and/or that the role of the hippocampus in remembering the last meal may diminish when the energy source is not novel and consumed habitually.…”

“…The present finding that sucrose ingestion increased dHC GluA1 pSer 831 is consistent with our previous results showing that sucrose ingestion elevates dHC expression of the plasticity-related immediate early gene activity-regulated cytoskeleton-associated protein ( Arc ) [71]. Of note, both GluA1 pSer 831 and Arc expression are dependent on activation of the glutamate NMDA receptor [72,73] and are critical for synaptic plasticity [74,75].…”

Ventral hippocampal neurons inhibit postprandial energy intake

“…One question that arises is whether they do so through similar or different underlying mechanisms. Our finding that sucrose ingestion increases Arc expression in both dHC (Henderson et al, ) and vHC (present findings) neurons is consistent with the possibility that both dHC and vHC neurons regulate intake through a process that involves memory. It is possible that dHC neurons encode the “what, where, and when” components of a recently eaten meal (Eichenbaum, ; Shapiro et al, ); whereas, vHC neurons encode the affective/emotional aspects (Fanselow and Dong, ; Strange et al, ).…”

“…Evidence from intact humans provides indirect support for the involvement of memory dysfunction, however, by showing that HC‐dependent memory does indeed influence future intake (Robinson et al, ). Moreover, satiety cues are likely needed to form a memory of a meal, which is supported by findings showing that postprandial signals such as leptin increase synaptic plasticity in HC (Shanley et al, ; Harvey et al, ), and by our findings showing that sucrose intake increases dHC (Henderson et al, ) and vHC Arc expression (present findings). Additional data are needed to resolve whether dHC and vHC inactivation‐induced increases in intake are due to impaired ability to detect interoceptive cues, a deficit in the interpretation or use of those cues, and/or impaired consolidation of the memory of the meal.…”

Ghrelin: A link between memory and ingestive behavior

“…Parent and colleagues (2013) have elegantly modeled this phenomenon in rodent models, demonstrating that reversible inactivation of hippocampal neurons immediately following a scheduled, anticipated sucrose meal reduces meal initiation latency and increases the size of the subsequent meal [26]. This group more recently demonstrated that orosensory stimulation through either intake of sucrose or non-caloric saccharin robustly increases hippocampal synpatic plasticity in an experience-dependent manner [27]. Together, these results suggest that 1) hippocampal neural processing can regulate the consolidation of food-related declarative memories, and 2) disrupted hippocampal processing can potentially lead to excessive eating.…”