Gaps in our understanding of how vagal afferents to the small intestinal mucosa detect luminal stimuli.

Vagal afferents to the gastrointestinal tract are crucial for the regulation of food intake, signaling negative feedback that contributes to satiation and positive feedback that produces appetition and reward. Vagal afferents to the small intestinal mucosa contribute to this regulation by sensing luminal stimuli and reporting this information to the brain. These afferents respond to mechanical, chemical, thermal, pH, and osmolar stimuli, as well as to bacterial products and immunogens. Surprisingly, little is known about how these stimuli are transduced by vagal mucosal afferents or how their transduction is organized among these afferents' terminals. Furthermore, the effects of stimulus concentration ranges or physiological stimuli on vagal activity have not been examined for some of these stimuli. Also, detection of luminal stimuli has rarely been examined in rodents, which are most frequently used for studying small intestinal innervation. Here we review what is known about stimulus detection by vagal mucosal afferents and illustrate the complexity of this detection using nutrients as an exemplar. The accepted model proposes that nutrients bind to taste receptors on enteroendocrine cells (EECs), which excite them, causing the release of hormones that stimulate vagal mucosal afferents. However, evidence reviewed here suggests that although this model accounts for many aspects of vagal signaling about nutrients, it cannot account for all aspects. A major goal of this review is therefore to evaluate what is known about nutrient absorption and detection and, based on this evaluation, identify candidate mucosal cells and structures that could cooperate with EECs and vagal mucosal afferents in stimulus detection.

Subacute Exposure to Gaseous Pollutants from Diesel Engine Exhaust Attenuates Capsaicin-Induced Cardio-Pulmonary Reflex Responses Involving Oxidant Stress Mechanisms in Adult Wistar Rats.

Intravenous injection of capsaicin produces vagal-mediated protective cardio-pulmonary (CP) reflexes manifesting as tachypnea, bradycardia, and triphasic blood pressure (BP) response in anesthetized rats. Particulate matter from diesel engine exhaust has been reported to attenuate these reflexes. However, the effects of gaseous constituents of diesel exhaust are not known. Therefore, the present study was designed to investigate the effects of gaseous pollutants in diesel exhaust, on capsaicin-induced CP reflexes in rat model. Adult male rats were randomly assigned to three groups: Non-exposed (NE) group, filtered diesel exhaust-exposed (FDE) group and N-acetyl cysteine (NAC)-treated FDE group. FDE group of rats (n = 6) were exposed to filtered diesel exhaust for 5 h a day for 5 days (D1-D5), and were taken for dissection on day 6 (D6), while NE group of rats (n = 6) remained unexposed. On D6, rats were anesthetized, following which jugular vein was cannulated for injection of chemicals, and femoral artery was cannulated to record the BP. Lead II electrocardiogram and respiratory movements were also recorded. Results show that intravenous injection of capsaicin (0.1 ml; 10 µg/kg) produced immediate tachypneic, hyperventilatory, hypotensive, and bradycardiac responses in both NE and FDE groups of rats. However, these capsaicin-induced CP responses were significantly attenuated in FDE group as compared to the NE group of rats. Further, FDE-induced attenuation of capsaicin-evoked CP responses were diminished in the N-acetyl cysteine-treated FDE rats. These findings demonstrate that oxidant stress mechanisms could possibly be involved in inhibition of CP reflexes by gaseous pollutants in diesel engine exhaust.

Vagal pathways for systemic regulation of glucose metabolism.

Maintaining blood glucose at an appropriate physiological level requires precise coordination of multiple organs and tissues. The vagus nerve bidirectionally connects the central nervous system with peripheral organs crucial to glucose mobilization, nutrient storage, and food absorption, thereby presenting a key pathway for the central control of blood glucose levels. However, the precise mechanisms by which vagal populations that target discrete tissues participate in glucoregulation are much less clear. Here we review recent advances unraveling the cellular identity, neuroanatomical organization, and functional contributions of both vagal efferents and vagal afferents in the control of systemic glucose metabolism. We focus on their involvement in relaying glucoregulatory cues from the brain to peripheral tissues, particularly the pancreatic islet, and by sensing and transmitting incoming signals from ingested food to the brain. These recent findings - largely driven by advances in viral approaches, RNA sequencing, and cell-type selective manipulations and tracings - have begun to clarify the precise vagal neuron populations involved in the central coordination of glucose levels, and raise interesting new possibilities for the treatment of glucose metabolism disorders such as diabetes.

Prox2 and Runx3 vagal sensory neurons regulate esophageal motility.

Vagal sensory neurons monitor mechanical and chemical stimuli in the gastrointestinal tract. Major efforts are underway to assign physiological functions to the many distinct subtypes of vagal sensory neurons. Here, we use genetically guided anatomical tracing, optogenetics, and electrophysiology to identify and characterize vagal sensory neuron subtypes expressing Prox2 and Runx3 in mice. We show that three of these neuronal subtypes innervate the esophagus and stomach in regionalized patterns, where they form intraganglionic laminar endings. Electrophysiological analysis revealed that they are low-threshold mechanoreceptors but possess different adaptation properties. Lastly, genetic ablation of Prox2 and Runx3 neurons demonstrated their essential roles for esophageal peristalsis in freely behaving mice. Our work defines the identity and function of the vagal neurons that provide mechanosensory feedback from the esophagus to the brain and could lead to better understanding and treatment of esophageal motility disorders.

Multiple sensor theory in airway mechanosensory units.

Two conventional doctrines govern airway mechanosensory interpretation: One-Sensor Theory (OST) and Line-Labeled Theory (LLT). In OST, one afferent fiber connects to a single sensor. In LLT, a different type of sensor sends signals via its specific line to a particular brain region to evoke its reflex. Thus, airway slowly adapting receptors (SARs) inhibit breathing and rapidly adapting receptors (RARs) stimulate breathing. However, recent studies show many different mechanosensors connect to a single afferent fiber (Multiple-Sensor Theory, MST). That is, SARs and RARs may send different types of information through the same afferent pathway, indicating different information has been integrated at the sensory unit level. Thus, a sensory unit is not merely a transducer (textbook concept), but also a processor. MST is a conceptual shift. Data generated over last eight decades under OST require re-interpretation.

Diabetes mellitus differently affects electrical membrane properties of vagal afferent neurons of rats.

To study whether diabetes mellitus (DM) would cause electrophysiological alterations in nodose ganglion (NG) neurons, we used patch clamp and intracellular recording for voltage and current clamp configuration, respectively, on cell bodies of NG from rats with DM. Intracellular microelectrodes recording, according to the waveform of the first derivative of the action potential, revealed three neuronal groups (A0 , Ainf , and Cinf ), which were differently affected. Diabetes only depolarized the resting potential of A0 (from -55 to -44 mV) and Cinf (from -49 to -45 mV) somas. In Ainf neurons, diabetes increased action potential and the after-hyperpolarization durations (from 1.9 and 18 to 2.3 and 32 ms, respectively) and reduced dV/dtdesc (from -63 to -52 V s-1 ). Diabetes reduced the action potential amplitude while increasing the after-hyperpolarization amplitude of Cinf neurons (from 83 and -14 mV to 75 and -16 mV, respectively). Using whole cell patch clamp recording, we observed that diabetes produced an increase in peak amplitude of sodium current density (from -68 to -176 pA pF-1 ) and displacement of steady-state inactivation to more negative values of transmembrane potential only in a group of neurons from diabetic animals (DB2). In the other group (DB1), diabetes did not change this parameter (-58 pA pF-1 ). This change in sodium current did not cause an increase in membrane excitability, probably explainable by the alterations in sodium current kinetics, which are also induced by diabetes. Our data demonstrate that diabetes differently affects membrane properties of different nodose neuron subpopulations, which likely have pathophysiological implications for diabetes mellitus.

Anatomical characterization of vagal nodose afferent innervation and ending morphologies at the murine heart using a transgenic approach.

Heart is an extensively innervated organ and its function is strictly coordinated by autonomic neural circuits. After pathological events such as myocardial infarction (MI), cardiac nerves undergo a structural and functional remodeling contributing to cardiac dysfunction. Although the efferent component of the cardiac nerves has been well described, sensory innervation of the heart has not been defined in detail. Considering its importance, comprehensive description of vagal afferent innervation on the whole heart would enable a better description of autonomic imbalances manifesting as sympathoexcitation and vagal withdrawal in post-ischemic states. To address this issue, we globally mapped the vagal nodose afferent fibers innervating the whole murine heart with unprecedented resolution. By using the Phox2b-Cre::tdTomato transgenic mouse line, we described the detailed distribution and distinct vagal sensory ending morphologies at both the dorsal and ventral sides of the mouse heart. By neural tracing analysis, we quantitated the distribution and prevalence of vagal afferent nerve fibers with varying diameters across dorsal and ventral surfaces of the heart. Moreover, we demonstrated that vagal afferents formed flower spray and end-net-like endings within the atria and ventricles. As distinct from the atria, vagal afferents formed intramuscular array-like endings within the ventricles. Furthermore, we showed that vagal afferents undergo structural remodeling by forming axonal sprouts around the infarct area in post-MI hearts. These findings improve our understanding of the potential effect of vagal afferent remodeling on autonomic imbalance and generation of cardiac arrhythmias and could prospectively contribute to the development of more effective neuromodulatory therapies.

Dietary Gamma-Aminobutyric Acid (GABA) Induces Satiation by Enhancing the Postprandial Activation of Vagal Afferent Nerves.

Gamma-aminobutyric acid (GABA) is present in the mammalian brain as the main inhibitory neurotransmitter and in foods. It is widely used as a supplement that regulates brain function through stress-reducing and sleep-enhancing effects. However, its underlying mechanisms remain poorly understood, as it is reportedly unable to cross the blood-brain barrier. Here, we explored whether a single peroral administration of GABA affects feeding behavior as an evaluation of brain function and the involvement of vagal afferent nerves. Peroral GABA at 20 and 200 mg/kg immediately before refeeding suppressed short-term food intake without aversive behaviors in mice. However, GABA administration 30 min before refeeding demonstrated no effects. A rise in circulating GABA concentrations by the peroral administration of 200 mg/kg GABA was similar to that by the intraperitoneal injection of 20 mg/kg GABA, which did not alter feeding. The feeding suppression by peroral GABA was blunted by the denervation of vagal afferents. Unexpectedly, peroral GABA alone did not alter vagal afferent activities histologically. The coadministration of a liquid diet and GABA potentiated the postprandial activation of vagal afferents, thereby enhancing postprandial satiation. In conclusion, dietary GABA activates vagal afferents in collaboration with meals or meal-evoked factors and regulates brain function including feeding behavior.

Bile acids induce Ca2+ signaling and membrane permeabilizations in vagal nodose ganglion neurons.

Bile acids (BAs) play an important role in the digestion of dietary fats and act as signaling molecules. However, due to their solubilizing properties, high concentrations in the gut may negatively affect gut epithelium and possibly afferent fibers innervating the gastrointestinal tract (GI). To determine the effect of BAs on intracellular Ca2+ and membrane permeabilization we tested a range of concentrations of two BAs on vagal nodose ganglion (NG) neurons, Chinese Hamster Ovary (CHO), and PC12 cell lines. NG explants from mice were drop-transduced with the genetically encoded Ca2+ indicator AAV9-Syn-jGCaMP7s and used to measure Ca2+ changes upon application of deoxycholic acid (DCA) and taurocholic acid (TCA). We found that both BAs induced a Ca2+ increase in NG neurons in a dose-dependent manner. The DCA-induced Ca2+ increase was dependent on intracellular Ca2+ stores. NG explants, with an intact peripheral part of the vagus nerve, showed excitation of NG neurons in nerve field recordings upon exposure to DCA. The viability of NG neurons at different BA concentrations was determined, and compared to CHO and PC12 cells lines using propidium iodide labeling, showing threshold concentrations of BA-induced cell death at 400-500 µM. These observations suggest that BAs act as Ca2+-inducing signaling molecules in vagal sensory neurons at low concentrations, but induce cell death at higher concentrations, which may occur during inflammatory bowel diseases.

A Novel Organ-Specific Approach to Selectively Target Sensory Afferents Innervating the Aortic Arch.

The brain maintains cardiovascular homeostasis, in part, via the arterial baroreflex which senses changes in blood pressure (BP) at the level of the aortic arch. Sensory afferents innervating the aortic arch employ baroreceptors to convert stretch exerted on the arterial wall into action potentials carried by the vagus nerve to second order neurons residing within the nucleus of the solitary tract (NTS). Although the baroreflex was described more than 80 years ago, the specific molecular, structural, and functional phenotype of the baroreceptors remain uncharacterized. This is due to the lack of tools that provide the genetic and target organ specificity that is required to selectively characterize baroreceptor afferents. Here, we use a novel approach to selectively target baroreceptors. Male mice on a C57BL/6J background were anesthetized with isoflurane, intubated, and artificially ventilated. Following sternotomy, the aortic arch was exposed, and a retrograde adeno-associated virus was applied to the aortic arch to direct the expression of channelrhoropsin-2 (ChR2) and/or tdTomato (tdTom) to sensory afferents presumably functioning as baroreceptors. Consistent with the structural characteristics of arterial baroreceptors, robust tdTom expression was observed in nerve endings surrounding the aortic arch, within the fibers of the aortic depressor and vagus nerves, cell bodies of the nodose ganglia (NDG), and neural projections to the caudal NTS (cNTS). Additionally, the tdTom labeled cell bodies within the NDG also expressed mRNAs coding for the mechanically gated ion channels, PIEZO-1 and PIEZO-2. In vitro electrophysiology revealed that pulses of blue light evoked excitatory post-synaptic currents in a subset of neurons within the cNTS, suggesting a functional connection between the labeled aortic arch sensory afferents and second order neurons. Finally, the in vivo optogenetic stimulation of the cell bodies of the baroreceptor expressing afferents in the NDG produced robust depressor responses. Together, these results establish a novel approach for selectively targeting sensory neurons innervating the aortic arch. This approach may be used to investigate arterial baroreceptors structurally and functionally, and to assess their role in the etiology or reversal of cardiovascular disease.

A comparative study of bronchopulmonary slowly adapting receptors between rabbits and rats.

Pulmonary mechanosensory receptors provide important inputs to the respiratory center for control of breathing. However, what is known about their structure-function relationship is still limited. In these studies, we explored this relationship comparing bronchopulmonary slowly adapting receptor (SAR) units in rabbits and rats. In morphological studies, sensory units in tracheobronchial smooth muscle labeled with anti-Na+ /K+ -ATPase (α3 subunit) were found to be larger in the rabbit. Since larger structures may result from increased receptor size or more numerous receptors, further examination showed receptor size was the same in both species, but more receptors in a structure in rabbits than rats, accounting for their larger structure. In functional studies, SAR units were recorded electrically in anesthetized, open-chest, and artificially ventilated animals and responses to lung inflation were compared at three different constant airway pressures (10, 20, and 30 cmH2 O). At each level of the inflation, SAR discharge frequencies were found to be higher in rabbits than rats. We conclude that a relatively larger number of receptors in a sensory unit may be responsible for higher SAR activities in rabbit SAR units.

Non-invasive vagus nerve stimulation boosts mood recovery after effort exertion.

BACKGROUND: Mood plays an important role in our life which is illustrated by the disruptive impact of aberrant mood states in depression. Although vagus nerve stimulation (VNS) has been shown to improve symptoms of depression, the exact mechanism is still elusive, and it is an open question whether non-invasive VNS could be used to swiftly and robustly improve mood. METHODS: Here, we investigated the effect of left- and right-sided transcutaneous auricular VNS (taVNS) v. a sham control condition on mood after the exertion of physical and cognitive effort in 82 healthy participants (randomized cross-over design) using linear mixed-effects and hierarchical Bayesian analyses of mood ratings. RESULTS: We found that 90 min of either left-sided or right-sided taVNS improved positive mood [b = 5.11, 95% credible interval, CI (1.39-9.01), 9.6% improvement relative to the mood intercept, BF10 = 7.69, pLME = 0.017], yet only during the post-stimulation phase. Moreover, lower baseline scores of positive mood were associated with greater taVNS-induced improvements in motivation [r = -0.42, 95% CI (-0.58 to -0.21), BF10 = 249]. CONCLUSIONS: We conclude that taVNS boosts mood after a prolonged period of effort exertion with concurrent stimulation and that acute motivational effects of taVNS are partly dependent on initial mood states. Collectively, our results show that taVNS may help quickly improve affect after a mood challenge, potentially by modulating interoceptive signals contributing to the reappraisal of effortful behavior. This suggests that taVNS could be a useful add-on to current behavioral therapies.

Paradoxical response of pulmonary slowly adapting units during constant pressure lung inflation.

Typically, unit discharge of slowly adapting receptors (SARs) declines slowly when lung inflation pressure is constant, although in some units it increases instead-a phenomenon hereinafter referred to as creeping. These studies characterize creeping behavior observed in 62 of 137 SAR units examined in anesthetized, open-chest, and mechanically ventilated rabbits. SAR units recorded from the cervical vagus nerve were studied during 4 s of constant lung inflation at 10, 20, and 30 cmH2O. Affected SAR units creep more quickly as inflation pressure increases. SAR units also often deactivate after creeping, i.e., their activity decreases or stops completely. Creeping likely results from encoder switching from a low discharge to a high discharge SAR, because it disappears in SAR units with multiple receptive fields after blocking a high discharge encoder in one field leaves low discharge encoders intact. The results support that encoder switching is a common mechanism operating in lung mechanosensory units.

Gastrointestinal Distension by Pectin-Containing Carbonated Solution Suppresses Food Intake and Enhances Glucose Tolerance via GLP-1 Secretion and Vagal Afferent Activation.

Diet-induced gastrointestinal distension is known to evoke satiation and suppress postprandial hyperglycemia; however, the underlying mechanisms remain poorly understood. This study explored how gastrointestinal distension regulates energy homeostasis by using inflating stomach formulation (ISF), the carbonated solution containing pectin that forms stable gel bubbles under acidic condition in the stomach. Here we show that, in mice, oral administration of ISF induced distension of stomach and proximal intestine temporarily, stimulated intestinal glucagon-like peptide-1 (GLP-1) secretion, and activated vagal afferents and brainstem. ISF suppressed food intake and improved glucose tolerance via enhancing insulin sensitivity. The anorexigenic effect was partially inhibited, and the beneficial glycemic effect was blunted by pharmacological GLP-1 receptor blockade and chemical denervation of capsaicin-sensitive sensory nerves. In HFD-fed obese mice showing arrhythmic feeding and obesity, subchronic ISF treatment at the light period (LP) onset for 10 days attenuated LP hyperphagia and visceral fat accumulation. These results demonstrate that gastrointestinal distension by ISF stimulates GLP-1 secretion and the vagal afferent signaling to the brain, thereby regulating feeding behavior and glucose tolerance. Furthermore, subchronic ISF treatment ameliorates HFD-induced visceral obesity. We propose the diet that induces gastrointestinal distension as a novel treatment of hyperphagic obesity and diabetes.

Gastrointestinal Vagal Afferents and Food Intake: Relevance of Circadian Rhythms.

Gastrointestinal vagal afferents (VAs) play an important role in food intake regulation, providing the brain with information on the amount and nutrient composition of a meal. This is processed, eventually leading to meal termination. The response of gastric VAs, to food-related stimuli, is under circadian control and fluctuates depending on the time of day. These rhythms are highly correlated with meal size, with a nadir in VA sensitivity and increase in meal size during the dark phase and a peak in sensitivity and decrease in meal size during the light phase in mice. These rhythms are disrupted in diet-induced obesity and simulated shift work conditions and associated with disrupted food intake patterns. In diet-induced obesity the dampened responses during the light phase are not simply reversed by reverting back to a normal diet. However, time restricted feeding prevents loss of diurnal rhythms in VA signalling in high fat diet-fed mice and, therefore, provides a potential strategy to reset diurnal rhythms in VA signalling to a pre-obese phenotype. This review discusses the role of the circadian system in the regulation of gastrointestinal VA signals and the impact of factors, such as diet-induced obesity and shift work, on these rhythms.

Vagally Mediated Gut-Brain Relationships in Appetite Control-Insights from Porcine Studies.

Signals arising from the upper part of the gut are essential for the regulation of food intake, particularly satiation. This information is supplied to the brain partly by vagal nervous afferents. The porcine model, because of its sizeable gyrencephalic brain, omnivorous regimen, and comparative anatomy of the proximal part of the gut to that of humans, has provided several important insights relating to the relevance of vagally mediated gut-brain relationships to the regulation of food intake. Furthermore, its large size combined with the capacity to become obese while overeating a western diet makes it a pivotal addition to existing murine models, especially for translational studies relating to obesity. How gastric, proximal intestinal, and portal information relating to meal arrival and transit are encoded by vagal afferents and their further processing by primary and secondary brain projections are reviewed. Their peripheral and central plasticities in the context of obesity are emphasized. We also present recent insights derived from chronic stimulation of the abdominal vagi with specific reference to the modulation of mesolimbic structures and their role in the restoration of insulin sensitivity in the obese miniature pig model.

Altered physiology of gastrointestinal vagal afferents following neurotrauma.

The adaptability of the central nervous system has been revealed in several model systems. Of particular interest to central nervous system-injured individuals is the ability for neural components to be modified for regain of function. In both types of neurotrauma, traumatic brain injury and spinal cord injury, the primary parasympathetic control to the gastrointestinal tract, the vagus nerve, remains anatomically intact. However, individuals with traumatic brain injury or spinal cord injury are highly susceptible to gastrointestinal dysfunctions. Such gastrointestinal dysfunctions attribute to higher morbidity and mortality following traumatic brain injury and spinal cord injury. While the vagal efferent output remains capable of eliciting motor responses following injury, evidence suggests impairment of the vagal afferents. Since sensory input drives motor output, this review will discuss the normal and altered anatomy and physiology of the gastrointestinal vagal afferents to better understand the contributions of vagal afferent plasticity following neurotrauma.

A historical perspective of pulmonary rapidly adapting receptors.

Bronchopulmonary mechanosensors play an important role in the regulation of breathing and airway defense. Regarding the mechanosensory unit, investigators have conventionally adhered to 2 doctrines: one-sensor theory (one afferent fiber connects to a single sensor) and line-labeled theory. Accordingly, lung inflation activates 2 types of mechanosensors: slowly adapting receptors (SARs) and rapidly adapting receptors (RARs) that also respond to lung deflation to produce Hering-Breuer deflation reflex. RARs send signals to a particular brain region to stimulate breathing (labeled as excitatory line) and SARs to a different region to inhibit breathing (inhibitory line). Conventionally, RARs are believed to be mechanosensors, but are also stimulated by a variety of chemicals and mediators. They are activated during different disease conditions and evoke various respiratory responses. In the literature, RARs are the most debatable sensors in the airway. Recent physiological and morphological studies demonstrate that a mechanosensory unit consists of numerous sensors with 4 types, i.e., an afferent fiber connects to multiple homogeneous or heterogeneous sensors (multiple-sensor theory). In addition to SARs and RARs, there are deflation-activated receptors (DARs), which can adapt slowly or rapidly. Each type senses a specific force and generates a unique response. For example, RAR (or SAR) units may respond to deflation if they house DARs responsible for the Hering-Breuer deflation reflex. Multiple-sensor theory requires a conceptual shift because 4 different types of information from numerous sensors carried in an afferent pathway violates conventional theories. Data generated over last eight decades under one-sensor theory require re-interpretation. Mechanosensors and their reflex functions need re-definition. This detailed review of the RARs represents our understanding of RARs under the conventional doctrines, thus it provides a very useful background for interpretation of RAR properties and reflex function against the new proposed multiple-sensor theory.

Pregnancy-related plasticity of gastric vagal afferent signals in mice.

Gastric vagal afferents (GVAs) sense food-related mechanical stimuli and signal to the central nervous system, to integrate control of meal termination. Pregnancy is characterized by increased maternal food intake, which is essential for normal fetal growth and to maximize progeny survival and health. However, it is unknown whether GVA function is altered during pregnancy to promote food intake. This study aimed to determine the mechanosensitivity of GVAs and food intake during early, mid-, and late stages of pregnancy in mice. Pregnant mice consumed more food compared with nonpregnant mice, notably in the light phase during mid- and late pregnancy. The increased food intake was predominantly due to light-phase increases in meal size across all stages of pregnancy. The sensitivity of GVA tension receptors to gastric distension was significantly attenuated in mid- and late pregnancy, whereas the sensitivity of GVA mucosal receptors to mucosal stroking was unchanged during pregnancy. To determine whether pregnancy-associated hormonal changes drive these adaptations, the effects of estradiol, progesterone, prolactin, and growth hormone on GVA tension receptor mechanosensitivity were determined in nonpregnant female mice. The sensitivity of GVA tension receptors to gastric distension was augmented by estradiol, attenuated by growth hormone, and unaffected by progesterone or prolactin. Together, the data indicate that the sensitivity of GVA tension receptors to tension is reduced during pregnancy, which may attenuate the perception of gastric fullness and explain increased food intake. Further, these adaptations may be driven by increases in maternal circulating growth hormone levels during pregnancy.NEW & NOTEWORTHY This study provides first evidence that gastric vagal afferent signaling is attenuated during pregnancy and inversely associated with meal size. Growth hormone attenuated mechanosensitivity of gastric vagal afferents, adding support that increases in maternal growth hormone may mediate adaptations in gastric vagal afferent signaling during pregnancy. These findings have important implications for the peripheral control of food intake during pregnancy.