Macronutrientes en el suelo y la planta

Decades of research on the neural controls of ingestive behavior has focused primarily on the role of homeostatic and hedonic processes; by contrast, there is a limited understanding of how brain areas involved in cognition inhibit energy intake. Investigating how brain areas involved in cognition limit eating will provide a more

complete explanation of the neural mechanisms that control ingestion and may enhance our understanding of eating‐related disorders such as obesity. Research in humans suggests that the encoding and maintenance of an episodic meal‐related memory limits future energy intake. For instance, enhancing the memory of a meal decreases the amount of food consumed during the subsequent eating episode (Robinson et

al., 2013a), whereas distraction during a meal results in greater feelings of hunger and increased consumption during the next bout (Brunstrom and Mitchell, 2006; Higgs and Woodward, 2009; Oldham‐Cooper et al., 2011). In addition, the memory of how much was consumed in a recently eaten meal is a better predictor of future hunger than the actual amount of food ingested (Brunstrom et al., 2012). Interestingly, the famous patient H.M. and others with severe episodic memory deficits do not remember having just eaten and will eat an additional meal if presented with food after eating to satiation (Hebben et al., 1985; Rozin et al., 1998; Higgs et al., 2008). Importantly, paying

attention to the food that is being consumed during a meal does not affect the size of that meal, but does decrease the amount consumed during the next eating bout in obese patients (Robinson et al., 2014).

The hippocampus is a brain structure essential for episodic learning and memory (Hunsaker et al., 2008; Kesner et al., 2008; Fanselow and Dong, 2010; Barbosa et

al., 2012; Strange et al., 2014). Neuroanatomical evidence suggests that the

hippocampus is also poised to integrate food‐related signals with mnemonic processing. Hippocampal neurons express receptors for several food‐related signals, such as leptin (Mercer et al., 1996), ghrelin, gastrin‐releasing peptide (a.k.a. bombesin; Kamichi et al., 2005), melanocortins (Mul et al., 2013; Shen et al., 2013), neuropeptide‐Y (Dumont et al., 1993), and cholecystokinin (Zarbin et al., 1983). Moreover, hippocampal neurons receive neural signals from multiple brain areas that communicate external sensory information and interoceptive cues about food (reviewed in Kanoski and Grill, 2015). In turn, hippocampal neurons project to several brain regions critical for food intake, such as the lateral hypothalamus (LH; Cenquizca and Swanson, 2006; Hsu et al., 2015b), bed nucleus of the stria terminalis (BSNT; Radley and Sawchenko, 2011), lateral septum (LS; Risold and Swanson, 1996, 1997), and nucleus accumbens (NA; Namura et al., 1994).

The hippocampus can be functionally divided along its longitudinal axis into dorsal (posterior in primates) and ventral (anterior in primates) poles (Moser and Moser, 1998; Fanselow and Dong, 2010; Strange et al., 2014). Generally, dorsal hippocampal (dHC) neurons are necessary for episodic and spatial memory, whereas ventral hippocampal (vHC) neurons are essential for affective and motivational

processes and emotional memory (Fanselow and Dong, 2010; Strange et al., 2014). Thus, both areas potentially contribute to the memory of eating episodes. In support, evidence suggests that both dHC and vHC are involved in energy regulation. For instance, we found previously that pharmacological inhibition of dHC neurons with infusions of the GABAA agonist muscimol given during the period following a sucrose

meal (i.e., the postprandial intermeal interval [ppIMI]; when the memory of the preceding meal would be expected to be undergoing consolidation) accelerates the onset of the next sucrose meal and increases the amount consumed during the next meal

(Henderson et al., 2013). We also found that consuming sucrose increases the expression of the immediate early gene activity‐regulated cytoskeleton‐associated‐ protein (Arc) in dHC neurons, suggesting that sucrose ingestion induces synaptic plasticity in dHC (Henderson et al., 2016). This interpretation is supported by previous research showing that a learning experience elevates hippocampal Arc expression and that these increases in Arc are necessary for memory consolidation in both dHC‐ and vHC‐dependent memory tasks (Guzowski et al., 2000; Plath et al., 2006; Bramham et al., 2010; Czerniawski et al., 2011; Shepherd and Bear, 2011; Czerniawski et al., 2012; Chia and Otto, 2013). Moreover, Arc expression is not a measure of neural activity (Fletcher et al., 2006; Guzowski et al., 2006); rather, the amount of Arc expressed is correlated with electrophysiological measures of synaptic plasticity (Carpenter‐Hyland et al., 2010). Collectively, our findings support the hypothesis that dHC neurons form a memory of a meal and reduce future intake.

Several lines of evidence have led us to hypothesize that vHC neurons also participate in forming a memory of an eating episode and inhibit energy intake during the period following intake (i.e., the ppIMI). Specifically, previous findings have shown that vHC lesions increase body weight and food consumption (Davidson et al., 2009) and that vHC infusions of the orexigenic hormone ghrelin increase food intake (Kanoski et al., 2013). In addition, activation of receptors for the gut hormones glucagon‐like peptide‐1 (GLP‐1) and leptin in vHC reduces food intake (Kanoski et al., 2011; Hsu et

al., 2015a), and vHC infusions of ghrelin, GLP‐1, and leptin also affect food‐related memory (Kanoski et al., 2011; Kanoski et al., 2013; Hsu et al., 2015a). Moreover, optogenetic activation of specific vHC projections to either BNST or LS markedly reduces total food consumption; whereas, chemogenetic inactivation of the dentate gyrus‐CA3 region of vHC increases energy intake (Sweeney and Yang, 2015). Importantly, vHC neurons are the primary source of hippocampal projections to brain regions critically involved in energy regulation such as LH, BNST, LS, and NA (Walaas and Fonnum, 1980; Kishi et al., 2000; Cenquizca and Swanson, 2006; Hsu et

al., 2015b).

Combined, these studies show that vHC neurons influence energy regulation; however, it is unknown whether vHC neurons regulate energy intake during the ppIMI when the memory of the meal is likely undergoing consolidation. As a result, the present study determined whether temporary inactivation of vHC neurons with infusions of muscimol given at the end of a sucrose meal accelerates the onset of the next meal and increases intake. If vHC neurons influence future intake through a process that involves memory, then ingestion should induce synaptic plasticity in these neurons. As a

molecular marker of plasticity, we also determined whether sucrose consumption increases Arc expression in vHC neurons.

2.3 Materials and Methods