Akihiko Kitamura

Effects of intragastric infusion of inosine monophosphate and l-glutamate on vagal gastric afferent activity and subsequent autonomic reflexes

In this study we investigated the effects of intragastric infusion of palatable basic taste substances (umami, sweet, and salty) on the activity of the vagal gastric afferent nerve (VGA), the vagal celiac efferent nerve (VCE), and the splanchnic adrenal efferent nerve (SAE) in anesthetized rats. To test the three selected taste groups, rats were infused with inosine monophosphate (IMP) and l-glutamate (GLU) for umami, with glucose and sucrose for sweet, and with sodium chloride (NaCl) for salty. Infusions of IMP and GLU solutions significantly increased VGA activity and induced the autonomic reflex, which activated VCE and SAE; these reflexes were abolished after sectioning of the VGA. Infusions of glucose, sucrose and NaCl solutions, conversely, had no significant effects on VGA activity. These results suggest that umami substances in the stomach send information through the VGA to the brain and play a role in the reflex regulation of visceral functions.

Detecting sweet and umami tastes in the gastrointestinal tract.

Information about nutrients is a critical part of food selection in living creatures. Each animal species has developed its own way to safely seek and obtain the foods necessary for them to survive and propagate. Necessarily, humans and other vertebrates have developed special chemosensory organs such as taste and olfactory organs. Much attention, recently, has been given to the gastrointestinal (GI) tract as another chemosensory organ. Although the GI tract had been considered to be solely for digestion and absorption of foods and nutrients, researchers have recently found taste‐signalling elements, including receptors, in this tissue. Further studies have revealed that taste cells in the oral cavity and taste‐like cells in the GI tract appear to share common characteristics. Major receptors to detect umami, sweet and bitter are found in the GI tract, and it is now proposed that taste‐like cells reside in the GI tract to sense nutrients and help maintain homeostasis. In this review, we summarize recent findings of chemoreception especially through sweet and umami sensors in the GI tract. In addition, the possibility of purinergic transmission from taste‐like cells in the GI tract to vagus nerves is discussed.

Correlation Between Activation of the Prelimbic Cortex, Basolateral Amygdala, and Agranular Insular Cortex During Taste Memory Formation

Conditioned taste aversion (CTA) is a well-established learning paradigm, whereby animals associate tastes with subsequent visceral illness. The prelimbic cortex (PL) has been shown to be involved in the association of events separated by time. However, the nature of PL activity and its functional network in the whole brain during CTA learning remain unknown. Here, using awake functional magnetic resonance imaging and fiber tracking, we analyzed functional brain connectivity during the association of tastes and visceral illness. The blood oxygen level-dependent (BOLD) signal significantly increased in the PL after tastant and lithium chloride (LiCl) infusions. The BOLD signal in the PL significantly correlated with those in the amygdala and agranular insular cortex (IC), which we found were also structurally connected to the PL by fiber tracking. To precisely examine these data, we then performed double immunofluorescence with a neuronal activity marker (c-Fos) and an inhibitory neuron marker (GAD67) combined with a fluorescent retrograde tracer in the PL. During CTA learning, we found an increase in the activity of excitatory neurons in the basolateral amygdala (BLA) or agranular IC that project to the PL. Taken together, these findings clearly identify a role of synchronized PL, agranular IC, and BLA activity in CTA learning.

The Sense of Taste in the Upper Gastrointestinal Tract

Digestion and the absorption of food and nutrients have been considered the only functions of the gastrointestinal (GI) tract. However, recent studies suggest that taste cells in the oral cavity and taste-like cells in the GI tract share many common characteristics (taste receptors and transduction signaling). Over the last two decades, it has been revealed that the GI tract is a chemosensory organ that transfers nutrient information via GI hormone secretion (glucagon-like peptide-1, Peptide YY, oxyntomodulin, glucose-dependent insulinotropic polypeptide and others) and the activation of abdominal vagus afferents. In addition, the information relayed via the abdominal vagus nerve plays an important role in autonomic reflexes. This information, both humoral and neural, contributes to the maintenance of homeostasis (digestion, absorption, metabolism and food intake) in the body. In this review, we provide a brief overview of the following: GI chemosensory molecules, their distribution, the effect of nutrients on GI hormone secretion and the activation of vagus afferent nerves. We also focus on the possibility of clinical applications that control abdominal vagus activity.

Biological Significance of Glutamate Signaling during Digestion of Food through the Gut-Brain Axis

Monosodium L-glutamate (MSG) elicits a unique taste termed umami and is widely used as a flavor enhancer in various cuisines. In addition, recent studies suggest the existence of sensors for L-glutamate (Glu) and transduction molecules in the gut mucosa as well as in the oral cavity. The vagal gastric afferent responds specifically to the luminal stimulation of Glu in the stomach and regulates the autonomic reflexes. The intragastric infusion of Glu also activates several brain areas (insular cortex, limbic system, and hypothalamus) and is able to induce flavor-preference learning in rats. These results suggest that umami signaling via gustatory and visceral pathways plays an important role in the processes of digestion, absorption, metabolism, and other physiological functions via activation of the brain.

Ingested d-Aspartate Facilitates the Functional Connectivity and Modifies Dendritic Spine Morphology in Rat Hippocampus

d-Aspartate (d-Asp), the stereoisomer of l-aspartate, has a role in memory function in rodents. However, the mechanism of the effect of d-Asp has not been fully understood. In this study, we hypothesized that ingested d-Asp directly reaches the hippocampal tissues via the blood circulation and modifies the functional connectivity between hippocampus and other regions through spinogenesis in hippocampal CA1 neurons. The spinogenesis induced by the application of d-Asp was investigated using rat acute hippocampal slices. The density of CA1 spines was increased following 21 and 100 μM d-Asp application. The nongenomic spine increase pathway involved LIM kinase. In parallel to the acute slice study, brain activation was investigated in awake rats using functional MRI following the intragastric administration of 5 mM d-Asp. Furthermore, the concentration of d-Asp in the blood serum and hippocampus was significantly increased 15 min after intragastric administration of d-Asp. A functional connectivity by awake rat fMRI demonstrated increased slow-frequency synchronization in the hippocampus and other regions, including the somatosensory cortex, striatum, and the nucleus accumbens, 10-20 min after the start of d-Asp administration. These results suggest that ingested d-Asp reaches the brain through the blood circulation and modulates hippocampal neural networks through the modulation of spines.