ABSTRACT
Linked rhythmic behaviors, such as respiration/locomotion or swallowing/chewing, often require coordination for proper function. Despite its prevalence, the cellular mechanisms controlling coordination of the underlying neural networks remain undetermined in most systems. We use the stomatogastric nervous system of the crab Cancer borealis to investigate mechanisms of internetwork coordination, due to its small, well-characterized feeding-related networks (gastric mill [chewing, â¼0.1â Hz]; pyloric [filtering food, â¼1â Hz]). Here, we investigate coordination between these networks during the Gly1-SIFamide neuropeptide modulatory state. Gly1-SIFamide activates a unique triphasic gastric mill rhythm in which the typically pyloric-only LPG neuron generates dual pyloric-plus gastric mill-timed oscillations. Additionally, the pyloric rhythm exhibits shorter cycles during gastric mill rhythm-timed LPG bursts, and longer cycles during IC, or IC plus LG gastric mill neuron bursts. Photoinactivation revealed that LPG is necessary to shorten pyloric cycle period, likely through its rectified electrical coupling to pyloric pacemaker neurons. Hyperpolarizing current injections demonstrated that although LG bursting enables IC bursts, only gastric mill rhythm bursts in IC are necessary to prolong the pyloric cycle period. Surprisingly, LPG photoinactivation also eliminated prolonged pyloric cycles, without changing IC firing frequency or gastric mill burst duration, suggesting that pyloric cycles are prolonged via IC synaptic inhibition of LPG, which indirectly slows the pyloric pacemakers via electrical coupling. Thus, the same dual-network neuron directly conveys excitation from its endogenous bursting and indirectly funnels synaptic inhibition to enable one network to alternately decrease and increase the cycle period of a related network.
Subject(s)
Brachyura , Ganglia, Invertebrate , Neurons , Neuropeptides , Animals , Brachyura/physiology , Neuropeptides/pharmacology , Neuropeptides/metabolism , Neurons/physiology , Neurons/drug effects , Ganglia, Invertebrate/physiology , Ganglia, Invertebrate/drug effects , Action Potentials/physiology , Action Potentials/drug effects , Nerve Net/physiology , Nerve Net/drug effects , Male , Feeding Behavior/physiology , Feeding Behavior/drug effects , Pylorus/physiology , Pylorus/drug effects , PeriodicityABSTRACT
OBJECTIVE: There has been recent clinical interest in the use of vagus nerve stimulation (VNS) for treating gastrointestinal disorders as an alternative to drugs or gastric electrical stimulation. However, effectiveness of burst stimulation has not been demonstrated. We investigated the ability of bursting and continuous VNS to influence gastric and pyloric activity under a range of stimulation parameters and gastric pressures. The goals of this study were to determine which parameters could optimally excite or inhibit gastric activity. MATERIALS AND METHODS: Data were collected from 21 Sprague-Dawley rats. Under urethane anesthesia, a rubber balloon was implanted into the stomach, connected to a pressure transducer and a saline infusion pump. A pressure catheter was inserted at the pyloric sphincter and a bipolar nerve cuff was implanted onto the left cervical vagus nerve. The balloon was filled to 15 cmH2O. Stimulation trials were conducted in a consistent order; the protocol was then repeated at 25 and 35 cmH2O. The nerve was then transected and stimulation repeated to investigate directionality of effects. RESULTS: Bursting stimulation at the bradycardia threshold caused significant increases in gastric contraction amplitude with entrainment to the bursting frequency. Some continuous stimulation trials could also cause increased contractions but without frequency changes. Few significant changes were observed at the pylorus, except for frequency entrainment. These effects could not be uniquely attributed to afferent or efferent activity. SIGNIFICANCE: Our findings further elucidate the effects of different VNS parameters on the stomach and pylorus and provide a basis for future studies of bursting stimulation for gastric neuromodulation.
Subject(s)
Muscle Contraction , Rats, Sprague-Dawley , Stomach , Vagus Nerve Stimulation , Animals , Vagus Nerve Stimulation/methods , Rats , Stomach/innervation , Stomach/physiology , Muscle Contraction/physiology , Male , Gastrointestinal Motility/physiology , Vagus Nerve/physiology , Pylorus/innervation , Pylorus/physiology , PressureABSTRACT
Oscillatory networks underlying rhythmic motor behaviors, and sensory and complex neural processing, are flexible, even in their neuronal composition. Neuromodulatory inputs enable neurons to switch participation between networks or participate in multiple networks simultaneously. Neuromodulation of internetwork synapses can both recruit and coordinate a switching neuron in a second network. We previously identified an example in which a neuron is recruited into dual-network activity via peptidergic modulation of intrinsic properties. We now ask whether the same neuropeptide also modulates internetwork synapses for internetwork coordination. The crab (Cancer borealis) stomatogastric nervous system contains two well-defined feeding-related networks (pyloric, food filtering, â¼1 Hz; gastric mill, food chewing, â¼0.1 Hz). The projection neuron MCN5 uses the neuropeptide Gly1-SIFamide to recruit the pyloric-only lateral posterior gastric (LPG) neuron into dual pyloric- plus gastric mill-timed bursting via modulation of LPG's intrinsic properties. Descending input is not required for a coordinated rhythm, thus intranetwork synapses between LPG and its second network must underlie coordination among these neurons. However, synapses between LPG and gastric mill neurons have not been documented. Using two-electrode voltage-clamp recordings, we found that graded synaptic currents between LPG and gastric mill neurons (lateral gastric, inferior cardiac, and dorsal gastric) were primarily negligible in saline, but were enhanced by Gly1-SIFamide. Furthermore, LPG and gastric mill neurons entrain each other during Gly1-SIFamide application, indicating bidirectional, functional connectivity. Thus, a neuropeptide mediates neuronal switching through parallel actions, modulating intrinsic properties for recruitment into a second network and as shown here, also modulating bidirectional internetwork synapses for coordination.NEW & NOTEWORTHY Neuromodulation can enable neurons to simultaneously coordinate with separate networks. Both recruitment into, and coordination with, a second network can occur via modulation of internetwork synapses. Alternatively, recruitment can occur via modulation of intrinsic ionic currents. We find that the same neuropeptide previously determined to modulate intrinsic currents also modulates bidirectional internetwork synapses that are typically ineffective. Thus, complementary modulatory peptide actions enable recruitment and coordination of a neuron into a second network.
Subject(s)
Brachyura , Neuropeptides , Synapses , Animals , Brachyura/physiology , Synapses/physiology , Neuropeptides/metabolism , Neuropeptides/pharmacology , Neurons/physiology , Ganglia, Invertebrate/physiology , Oligopeptides/pharmacology , Nerve Net/physiology , Pylorus/physiology , Male , Action Potentials/physiologyABSTRACT
Network flexibility is important for adaptable behaviors. This includes neuronal switching, where neurons alter their network participation, including changing from single- to dual-network activity. Understanding the implications of neuronal switching requires determining how a switching neuron interacts with each of its networks. Here, we tested 1) whether "home" and second networks, operating via divergent rhythm generation mechanisms, regulate a switching neuron and 2) if a switching neuron, recruited via modulation of intrinsic properties, contributes to rhythm or pattern generation in a new network. Small, well-characterized feeding-related networks (pyloric, â¼1 Hz; gastric mill, â¼0.1 Hz) and identified modulatory inputs make the isolated crab (Cancer borealis) stomatogastric nervous system (STNS) a useful model to study neuronal switching. In particular, the neuropeptide Gly1-SIFamide switches the lateral posterior gastric (LPG) neuron (2 copies) from pyloric-only to dual-frequency pyloric/gastric mill (fast/slow) activity via modulation of LPG-intrinsic properties. Using current injections to manipulate neuronal activity, we found that gastric mill, but not pyloric, network neurons regulated the intrinsically generated LPG slow bursting. Conversely, selective elimination of LPG from both networks using photoinactivation revealed that LPG regulated gastric mill neuron-firing frequencies but was not necessary for gastric mill rhythm generation or coordination. However, LPG alone was sufficient to produce a distinct pattern of network coordination. Thus, modulated intrinsic properties underlying dual-network participation may constrain which networks can regulate switching neuron activity. Furthermore, recruitment via intrinsic properties may occur in modulatory states where it is important for the switching neuron to actively contribute to network output.NEW & NOTEWORTHY We used small, well-characterized networks to investigate interactions between rhythmic networks and neurons that switch their network participation. For a neuron switching into dual-network activity, only the second network regulated its activity in that network. In addition, the switching neuron was sufficient but not necessary to coordinate second network neurons and regulated their activity levels. Thus, regulation of switching neurons may be selective, and a switching neuron is not necessarily simply a follower in additional networks.
Subject(s)
Brachyura , Neurons , Animals , Neurons/physiology , Pylorus/physiology , Brachyura/physiology , Ganglia, Invertebrate/physiology , Periodicity , Nerve Net/physiologyABSTRACT
Nervous systems have evolved to function consistently in the face of the normal environmental fluctuations experienced by animals. The stomatogastric nervous system (STNS) of the crab, Cancer borealis, produces a motor output that has been studied for its remarkable robustness in response to single global perturbations. Changes in environments, however, are often complex and multifactorial. Therefore, we studied the robustness of the pyloric network in the stomatogastric ganglion (STG) in response to simultaneous perturbations of temperature and pH. We compared the effects of elevated temperatures on the pyloric rhythm at control, acid, or base pHs. In each pH recordings were made at 11°C, and then the temperature was increased until the rhythms became disorganized ("crashed"). Pyloric burst frequencies and phase relationships showed minor differences between pH groups until reaching close to the crash temperatures. However, the temperatures at which the rhythms were disrupted were lower in the two extreme pH conditions. This indicates that one environmental stress can make an animal less resilient to a second stressor.NEW & NOTEWORTHY Resilience to environmental fluctuations is important for all animals. It is common that animals encounter multiple stressful events at the same time, the cumulative impacts of which are largely unknown. This study examines the effects of temperature and pH on the nervous system of crabs that live in the fluctuating environments of the Northern Atlantic Ocean. The ranges of tolerance to one perturbation, temperature, are reduced under the influence of a second, pH.
Subject(s)
Brachyura , Pylorus , Animals , Temperature , Pylorus/physiology , Ganglia, Invertebrate/physiology , Brachyura/physiologyABSTRACT
The common occurrence of gastric disorders, the accelerating emphasis on the role of the gut-brain axis, and development of realistic, predictive models of gastric function, all place emphasis on increasing understanding of the stomach and its control. However, the ways that regions of the stomach have been described anatomically, physiologically, and histologically do not align well. Mammalian single compartment stomachs can be considered as having four anatomical regions fundus, corpus, antrum, and pyloric sphincter. Functional regions are the proximal stomach, primarily concerned with adjusting gastric volume, the distal stomach, primarily involved in churning and propelling the content, and the pyloric sphincter that regulates passage of chyme into the duodenum. The proximal stomach extends from the dome of the fundus to a circumferential band where propulsive waves commence (slow waves of the pacemaker region), and the distal stomach consists of the pacemaker region and the more distal regions that are traversed by waves of excitation, that travel as far as the pyloric sphincter. Thus, the proximal stomach includes the fundus and different extents of the corpus, whereas the distal stomach consists of the remainder of the corpus and the antrum. The distributions of aglandular regions and of specialized glands, such as oxyntic glands, differ vastly between species and, across species, have little or no relation to anatomical or functional regions. It is hoped that this review helps to clarify nomenclature that defines gastric regions that will provide an improved basis for drawing conclusions for different investigations of the stomach.
Subject(s)
Stomach Diseases , Stomach , Animals , Stomach/physiology , Pylorus/physiology , Gastric Fundus/physiology , Duodenum/physiology , Pyloric Antrum/physiology , MammalsABSTRACT
The main function of the stomach is to digest ingested food. Gastric antrum muscular contractions mix ingested food with digestive enzymes and stomach acid and propel the chyme through the pyloric sphincter at a rate in which the small intestine can process the chyme for optimal nutrient absorption. Mfge8 binding to α8ß1 integrins helps regulate gastric emptying by reducing the force of antral smooth muscle contractions. The source of Mfge8 within gastric muscles is unclear. Since Mfge8 is a secreted protein, Mfge8 could be delivered via the circulation, or be locally secreted by cells within the muscle layers. In this study, we identify a source of Mfge8 within human gastric antrum muscles using spatial transcriptomic analysis. We show that Mfge8 is expressed in subpopulations of Mef2c+ perivascular cells within the submucosa layer of the gastric antrum. Mef2c is expressed in subpopulations of NG2+ and PDGFRB+ pericytes. Mfge8 is expressed in NG2+/Mef2c+ pericytes, but not in NG2+/Mef2c-, PDGFRB+/Mef2c-, or PDGFRB+/Mef2c+ pericytes. Mfge8 is absent from CD34+ endothelial cells but is expressed in a small population of perivascular ACTA2+ cells. We also show that α8 integrin is not expressed by interstitial cells of Cajal (ICC), supporting the findings that Mfge8 attenuates gastric antrum smooth muscle contractions by binding to α8ß1 integrins on enteric smooth muscle cells. These findings suggest a novel, supplementary mechanism of regulation of gastric antrum motility by cellular regulators of capillary blood flow, in addition to the regulation of gastric antrum motility by the enteric nervous system and the SMC, ICC, and PDGFRα+ cell (SIP) syncytium.
Subject(s)
Pericytes , Pyloric Antrum , Humans , Pyloric Antrum/metabolism , Endothelial Cells , Receptor, Platelet-Derived Growth Factor beta/metabolism , Pylorus/physiology , Gastric Emptying/physiology , Integrins/metabolism , Obesity/metabolism , Antigens, Surface/metabolism , Milk Proteins/metabolismABSTRACT
This chapter reviews data on the pathways by which luminal, mainly duodenal, chemoreceptors modulate gastro-pyloro-duodenal motor function to control emptying of nutrients into the small intestine. The vagus mediates proximal gastric relaxation caused by nutrient stimulation of duodenal/jejunal mucosal chemoreceptors. Modulation of the spatial patterning and inhibition of antral contractions during duodenal chemoreceptor activation are somewhat conflicting: both vagal control and ascending intramural nerves appear to play a role. Intraduodenal nutrients stimulate the localized pyloric contractions that prevent transpyloric flow via ascending duodenal intramural nerve pathways. Though not yet formally investigated, patterns of activation of the duodenal brake motor mechanism suggest that duodenal loop mucosal chemoreceptors signal to a brake mechanism at the most aborad region of the duodenum via descending intramural duodenal nerves.Intrinsic intramural pathways are important in the control of the first stages of digestion.
Subject(s)
Gastrointestinal Motility , Pyloric Antrum , Pyloric Antrum/innervation , Pyloric Antrum/physiology , Gastrointestinal Motility/physiology , Pylorus/physiology , Duodenum/innervation , Duodenum/physiology , Intestine, SmallABSTRACT
Neural network flexibility includes changes in neuronal participation between networks, such as the switching of neurons between single- and dual-network activity. We previously identified a neuron that is recruited to burst in time with an additional network via modulation of its intrinsic membrane properties, instead of being recruited synaptically into the second network. However, the modulated intrinsic properties were not determined. Here, we use small networks in the Jonah crab (Cancer borealis) stomatogastric nervous system (STNS) to examine modulation of intrinsic properties underlying neuropeptide (Gly1-SIFamide)-elicited neuronal switching. The lateral posterior gastric neuron (LPG) switches from exclusive participation in the fast pyloric (â¼1 Hz) network, due to electrical coupling, to dual-network activity that includes periodic escapes from the fast rhythm via intrinsically generated oscillations at the slower gastric mill network frequency (â¼0.1 Hz). We isolated LPG from both networks by pharmacology and hyperpolarizing current injection. Gly1-SIFamide increased LPG intrinsic excitability and rebound from inhibition and decreased spike frequency adaptation, which can all contribute to intrinsic bursting. Using ion substitution and channel blockers, we found that a hyperpolarization-activated current, a persistent sodium current, and calcium or calcium-related current(s) appear to be primary contributors to Gly1-SIFamide-elicited LPG intrinsic bursting. However, this intrinsic bursting was more sensitive to blocking currents when LPG received rhythmic electrical coupling input from the fast network than in the isolated condition. Overall, a switch from single- to dual-network activity can involve modulation of multiple intrinsic properties, while synaptic input from a second network can shape the contributions of these properties.NEW & NOTEWORTHY Neuropeptide-elicited intrinsic bursting was recently determined to switch a neuron from single- to dual-network participation. Here we identified multiple intrinsic properties modulated in the dual-network state and candidate ion channels underlying the intrinsic bursting. Bursting at the second network frequency was more sensitive to blocking currents in the dual-network state than when neurons were synaptically isolated from their home network. Thus, synaptic input can shape the contributions of modulated intrinsic properties underlying dual-network activity.
Subject(s)
Brachyura , Neuropeptides , Animals , Calcium , Neurons/physiology , Pylorus/physiologyABSTRACT
The levels of voltage-gated and synaptic currents in the same neuron type can vary substantially across individuals. Yet, the phase relationships between neurons in oscillatory circuits are often maintained, even in the face of varying oscillation frequencies. We examined whether synaptic and intrinsic currents are matched to maintain constant activity phases across preparations, using the lateral pyloric (LP) neuron of the stomatogastric ganglion (STG) of the crab, Cancer borealis LP produces stable oscillatory bursts on release from inhibition, with an onset phase that is independent of oscillation frequency. We quantified the parameters that define the shape of the synaptic current inputs across preparations and found no linear correlations with voltage-gated currents. However, several synaptic parameters were correlated with oscillation period and burst onset phase, suggesting they may play a role in phase maintenance. We used dynamic clamp to apply artificial synaptic inputs and found that those synaptic parameters correlated with phase and period were ineffective in influencing burst onset. Instead, parameters that showed the least variability across preparations had the greatest influence. Thus, parameters that influence circuit phasing are constrained across individuals, while those that have little effect simply co-vary with phase and frequency.
Subject(s)
Brachyura , Ganglia, Invertebrate , Animals , Ganglia , Ganglia, Invertebrate/physiology , Neurons/physiology , Pylorus/physiologyABSTRACT
Delayed gastric emptying may result from diverse pathophysiological mechanisms including antral hypomotility and pylorospasm. With increasing use of gastric peroral endoscopic myotomy and preliminary evidence of efficacy, our aim was to assess the motor functions of the distal antrum and pylorus in patients with symptoms of gastroparesis using high-resolution antropyloroduodenal manometry (HR-ADM). Sixteen patients with symptoms suggestive of gastroparesis underwent HR-ADM with 13 sensors, 1 cm apart, placed across the antropyloroduodenal (APD) junction and 2 sensors, 10 cm apart, in descending and distal duodenum. The 1-h postprandial motility was quantitated as contraction frequency/minute, average amplitude, and motility index (MI). Six healthy volunteers served as controls. In the patient group, the HR-ADM identified postprandial antral hypomotility, isolated pyloric pressure waves, and tonic elevation of baseline pressure in pylorus. Patients had significantly reduced frequency of the full-hour postprandial antral contractions/minute compared with healthy volunteers [1.52 (0.97, 1.67) vs. 2.04 (1.70, 2.67), P = 0.005], as well as reduced MI [9.65 (8.29, 10.31) vs. 11.04 (10.65, 11.63), P = 0.002]. The average contraction amplitude was numerically, but not significantly reduced [51.9 (21.9, 74.9) vs. 73.0 (59.8, 82.7), P = 0.14]. Bland-Altman plots showed similar distribution of antral contraction frequency and MI during the first and second postprandial 30-min periods for both patients and controls. High-resolution ADM can characterize a variety of postprandial antral contractile and pyloric motility dysfunctions. This technique shows promise to provide guidance for the selection of optimal treatment of patients with gastroparesis.NEW & NOTEWORTHY Current selection of different treatments for patients with gastroparesis is empiric or based on trial and error, though pyloric distensibility and diameter may predict response to pyloric interventions. High-resolution antropyloroduodenal manometry (HR-ADM) can characterize a variety of postprandial antral contractile and pyloric motility dysfunctions in patients with suspected gastroparesis. HR-ADM shows promise to provide guidance for selection and individualization of treatments such as prokinetic agents or pyloric interventions for patients with gastroparesis based on documented pathophysiology.
Subject(s)
Esophageal Achalasia , Gastroparesis , Duodenum/physiology , Esophageal Sphincter, Lower , Gastric Emptying , Gastrointestinal Motility/physiology , Gastroparesis/diagnosis , Humans , Manometry/methods , Pyloric Antrum/physiology , Pylorus/physiologyABSTRACT
Neural circuits can generate many spike patterns, but only some are functional. The study of how circuits generate and maintain functional dynamics is hindered by a poverty of description of circuit dynamics across functional and dysfunctional states. For example, although the regular oscillation of a central pattern generator is well characterized by its frequency and the phase relationships between its neurons, these metrics are ineffective descriptors of the irregular and aperiodic dynamics that circuits can generate under perturbation or in disease states. By recording the circuit dynamics of the well-studied pyloric circuit in Cancer borealis, we used statistical features of spike times from neurons in the circuit to visualize the spike patterns generated by this circuit under a variety of conditions. This approach captures both the variability of functional rhythms and the diversity of atypical dynamics in a single map. Clusters in the map identify qualitatively different spike patterns hinting at different dynamic states in the circuit. State probability and the statistics of the transitions between states varied with environmental perturbations, removal of descending neuromodulatory inputs, and the addition of exogenous neuromodulators. This analysis reveals strong mechanistically interpretable links between complex changes in the collective behavior of a neural circuit and specific experimental manipulations, and can constrain hypotheses of how circuits generate functional dynamics despite variability in circuit architecture and environmental perturbations.
Subject(s)
Brachyura , Ganglia, Invertebrate , Animals , Brachyura/physiology , Ganglia, Invertebrate/physiology , Neurons/physiology , Neurotransmitter Agents/physiology , Pylorus/physiologyABSTRACT
Until recently, gastric motility measurements in humans were mostly limited to accommodation (using barostat or 3-dimensional imaging studies of gastric volume) and gastric emptying tests, the latter being the only one performed in routine clinical care. Accurate and easy to use techniques were lacking to assess pyloric function in health and disease. Recently, pyloric distensibility has been developed and validated to assess pyloric opening. Several studies confirmed that pyloric distensibility was decreased in gastroparesis and correlated with gastric emptying as well as gastroparesis symptoms. In addition, pyloric distensibility may predict outcome of endoscopic techniques targeting the pylorus, namely intrapyloric botulinum toxin injection and gastric per-oral pyloromyotomy. Pyloric distensibility appears therefore to be a promising and useful new tool in the workup of gastroparesis patients.
Subject(s)
Gastroparesis/physiopathology , Pylorus/physiology , Animals , Gastric Emptying , Gastroparesis/diagnostic imaging , Gastroparesis/surgery , Humans , Pyloromyotomy/methods , Pylorus/physiopathologyABSTRACT
Nowadays, in vitro digestion models have received growing interest in recent years to track the digestive fate of foods in the gastrointestinal tract. A major challenge in the development of more physiologically relevant in vitro gastric models is to simulate realistic gastric emptying. In this study, an advanced dynamic in vitro human gastric system was investigated for its potential in achieving the above. The mechanisms for controlling the gastric emptying rate by modulations of the peristaltic moving distance, the pylorus opening size/frequency, and the stomach tilting angle in relation to time are illustrated. With solid cheese, a difficult food material for emptying, different combinations of the operational parameters of the stomach system were evaluated. The system was steered to attain consistent gastric emptying curve with the theoretical data by optimizing operational parameters. By fitting the gastric retention data with a power-exponential model, which is a common approach for describing gastric emptying, the total meal achieved an average emptying half-time (t1/2) of 84.5 min and a curve shape coefficient (ß) of 1.69, similar to the theoretical data reported in the literature, where the values of t1/2 and ß were 85 min and 1.8, respectively (p > 0.05). Furthermore, the mean median particle size was significantly decreased from the initial 2.80 mm (cheese cubes) to the final 1.35 mm (p < 0.05). There are few particles greater than 2 mm observed in the emptied cheese digesta throughout the digestion process. These suggest the powerful gastric grinding and sieving capacity exhibited by the in vitro system. The current study demonstrates that a well-considered in vitro system can offer a reasonable approach for tracking the structural and physicochemical changes of foods during digestion in the stomach, which is practically meaningful.
Subject(s)
Cheese , Digestion , Gastric Emptying , Humans , Hydrogen-Ion Concentration , In Vitro Techniques , Models, Biological , Particle Size , Peristalsis , Pylorus/physiology , Stomach/physiologyABSTRACT
Coupled oscillatory circuits are ubiquitous in nervous systems. Given that most biological processes are temperature-sensitive, it is remarkable that the neuronal circuits of poikilothermic animals can maintain coupling across a wide range of temperatures. Within the stomatogastric ganglion (STG) of the crab, Cancer borealis, the fast pyloric rhythm (~1 Hz) and the slow gastric mill rhythm (~0.1 Hz) are precisely coordinated at ~11°C such that there is an integer number of pyloric cycles per gastric mill cycle (integer coupling). Upon increasing temperature from 7°C to 23°C, both oscillators showed similar temperature-dependent increases in cycle frequency, and integer coupling between the circuits was conserved. Thus, although both rhythms show temperature-dependent changes in rhythm frequency, the processes that couple these circuits maintain their coordination over a wide range of temperatures. Such robustness to temperature changes could be part of a toolbox of processes that enables neural circuits to maintain function despite global perturbations.
Subject(s)
Brachyura/physiology , Periodicity , Animals , Cold Temperature , Gizzard, Non-avian/physiology , Hot Temperature , Male , Pylorus/physiologyABSTRACT
Peroral pyloromyotomy, an innovative intramural endoscopic surgery procedure, is a successful management option for appropriately selected patients who suffer from medically refractory gastroparesis. Gastroparesis is a debilitating disorder of the gastrointestinal tract, which significantly decreases quality of life and overall survival. This article describes the history and background, the indications for, the diagnosis of, and the preparation, technique, and short-term outcomes of peroral pyloromyotomy.
Subject(s)
Gastroparesis/surgery , Pyloromyotomy , Combined Modality Therapy , Gastroparesis/diagnosis , Gastroparesis/therapy , Humans , Patient Care Team , Perioperative Care , Pyloromyotomy/methods , Pyloromyotomy/standards , Pylorus/anatomy & histology , Pylorus/physiology , Pylorus/physiopathologyABSTRACT
AIMS: Our main goal is to study the effects on the carbohydrate metabolism. Thus, we designed various experimental surgical models on healthy non-obese Wistar rats to reproduce several conditions. In this sense, we report a new experimental model. It is well known that bariatric surgery has important effects on the control of Type 2 Diabetes Mellitus. The underlying reasons are yet unknown, although the different theories focused in the release of different hormones after the pass of the nutrients through the tract. These released hormones have opposite effects that come together in a balanced glycemic metabolism. MATERIALS AND METHODS: After bariatric surgical techniques, the modified anatomy resulted in an imbalance of the secreted hormones. Wistar rats were randomized in two groups Sham and surgical group. Our model consisted on the transposition of the terminal ileum right after the pylorus. Weight gain, food intake, and basal glycemia were measured weekly. RESULTS: We did not obtain significant differences between both groups for these functional variables. CONCLUSIONS: This technique involved an early pass of the bolus through the ileum. The change on the luminal pH, along with the lack of enzymes to absorb the content, or the changes in the release of several hormones must be variables to the study. The mortality rate was assumable considering it was an experimental model on animals.
OBJETIVO: Crear un nuevo modelo quirúrgico experimental en ratas Wistar sanas no obesas para estudiar los efectos del metabolismo glucídico. Es bien sabido que las técnicas de cirugía bariátrica tienen un efecto importante sobre la resolución de la diabetes mellitus tipo 2. Se han invocado diferentes hipótesis, algunas centradas en el papel que tienen distintas hormonas secretadas por el propio tubo digestivo tras el paso de los nutrientes a su través, pero las razones últimas subyacentes permanecen desconocidas. El efecto contrapuesto de dichas hormonas consigue un efecto de control glucémico. El desequilibrio hormonal tras las alteraciones anatómicas de las cirugías bariátricas podría estar en la base de dicha mejora del metabolismo glucídico final. MATERIAL Y MÉTODOS: Las ratas fueron operadas en dos grupos (control quirúrgico y experimental) y se procedió a disponerles el íleon anastomosado al antro pilórico, previo al esfínter pilórico. Medimos distintos parámetros funcionales (ganancia de peso, ingesta y glucemias semanales). RESULTADOS: No obtuvimos diferencias significativas en la evolución de estos parámetros. CONCLUSIONES: Este modelo será útil para nuestro propósito de estudiar el íleon, en su componente secretor de enterohormonas, cuando el paso de los nutrientes se produzca tempranamente. La mortalidad fue asumible, dada la innovación técnica realizada.
Subject(s)
Blood Glucose/metabolism , Duodenum/surgery , Gastrointestinal Transit/physiology , Ileum/surgery , Models, Animal , Anastomosis, Surgical/methods , Anastomosis, Surgical/mortality , Animals , Bariatric Surgery/methods , Bariatric Surgery/mortality , Blood Glucose/analysis , Carbohydrate Metabolism , Diabetes Mellitus, Type 2/metabolism , Duodenum/physiology , Eating , Ileum/physiology , Incretins/metabolism , Male , Pylorus/physiology , Random Allocation , Rats , Rats, Wistar , Weight GainABSTRACT
Elevated potassium concentration ([K+]) is often used to alter excitability in neurons and networks by shifting the potassium equilibrium potential (EK) and, consequently, the resting membrane potential. We studied the effects of increased extracellular [K+] on the well-described pyloric circuit of the crab Cancer borealis. A 2.5-fold increase in extracellular [K+] (2.5×[K+]) depolarized pyloric dilator (PD) neurons and resulted in short-term loss of their normal bursting activity. This period of silence was followed within 5-10 min by the recovery of spiking and/or bursting activity during continued superfusion of 2.5×[K+] saline. In contrast, when PD neurons were pharmacologically isolated from pyloric presynaptic inputs, they exhibited no transient loss of spiking activity in 2.5×[K+], suggesting the presence of an acute inhibitory effect mediated by circuit interactions. Action potential threshold in PD neurons hyperpolarized during an hour-long exposure to 2.5×[K+] concurrent with the recovery of spiking and/or bursting activity. Thus the initial loss of activity appears to be mediated by synaptic interactions within the network, but the secondary adaptation depends on changes in the intrinsic excitability of the pacemaker neurons. The complex sequence of events in the responses of pyloric neurons to elevated [K+] demonstrates that electrophysiological recordings are necessary to determine both the transient and longer term effects of even modest alterations of K+ concentrations on neuronal activity.NEW & NOTEWORTHY Solutions with elevated extracellular potassium are commonly used as a depolarizing stimulus. We studied the effects of high potassium concentration ([K+]) on the pyloric circuit of the crab stomatogastric ganglion. A 2.5-fold increase in extracellular [K+] caused a transient loss of activity that was not due to depolarization block, followed by a rapid increase in excitability and recovery of spiking within minutes. This suggests that changing extracellular potassium can have complex and nonstationary effects on neuronal circuits.
Subject(s)
Brachyura/physiology , Central Pattern Generators/physiology , Electrophysiological Phenomena/physiology , Ganglia, Invertebrate/physiology , Potassium/metabolism , Pylorus/physiology , Animals , Central Pattern Generators/metabolism , Ganglia, Invertebrate/metabolism , Male , Pylorus/metabolismABSTRACT
BACKGROUND: Vagus nerve stimulation (VNS) is an emerging bioelectronic therapy for regulating food intake and controlling gastric motility. However, the effects of different VNS parameters and polarity on postprandial gastric motility remain incompletely characterized. METHODS: In anesthetized rats (N = 3), we applied monophasic electrical stimuli to the left cervical vagus and recorded compound nerve action potential (CNAP) as a measure of nerve response. We evaluated to what extent afferent or efferent pathway could be selectively activated by monophasic VNS. In a different group of rats (N = 13), we fed each rat a gadolinium-labeled meal and scanned the rat stomach with oral contrast-enhanced magnetic resonance imaging (MRI) while the rat was anesthetized. We evaluated the antral and pyloric motility as a function of pulse amplitude (0.13, 0.25, 0.5, 1 mA), width (0.13, 0.25, 0.5 ms), frequency (5, 10 Hz), and polarity of VNS. KEY RESULTS: Monophasic VNS activated efferent and afferent pathways with about 67% and 82% selectivity, respectively. Primarily afferent VNS increased antral motility across a wide range of parameters. Primarily efferent VNS induced a significant decrease in antral motility as the stimulus intensity increased (R = -.93, P < .05 for 5 Hz, R = -.85, P < .05 for 10 Hz). The VNS with either polarity tended to promote pyloric motility to a greater extent given increasing stimulus intensity. CONCLUSIONS AND INFERENCES: Monophasic VNS biased toward the afferent pathway is potentially more effective for facilitating occlusive contractions than that biased toward the efferent pathway.
Subject(s)
Duodenum/physiology , Gastrointestinal Motility , Pyloric Antrum/physiology , Pylorus/physiology , Vagus Nerve Stimulation/methods , Vagus Nerve/physiology , Action Potentials , Afferent Pathways/physiology , Animals , Duodenum/innervation , Efferent Pathways/physiology , Magnetic Resonance Imaging , Male , Pyloric Antrum/innervation , Pylorus/innervation , Rats, Sprague-DawleyABSTRACT
Transplantation of neural stem cells is a promising approach in treatment of intestinal dysfunctionality. The interstitial cells of Cajal (ICCs) are also critical in conditions such as pyloric dysfunctionality and gastroparesis. The objective of this study was to replenish neurons and ICCs in a dysfunctional pylorus as cell-based therapy to restore functionality. ICCs and enteric neural progenitor cells (NPCs) were isolated from rat duodenum and transduced with fluorescent proteins. Rat pylorus was harvested, and an ex-vivo neuromuscular dysfunctional model was developed by selective ablation of neurons and ICCs via chemical treatments. Cellular repopulation and restoration of motility were assessed by immunohistochemistry, qPCR, and functional analysis after delivery of fluorescently tagged cells. Chemical treatment of pylorus resulted in significant depletion of ICCs (67%, P = .0024; n = 3) and neural cells (83%, P = .0012; n = 3). Delivered ICCs and NPCs survived and integrated with host muscle layers. Co-injection of ICCs with NPCs exhibited 34.4% (P = .0004; n = 3) and 61.0% (P = .0003; n = 3) upregulation of ANO1 and ßIII tubulin, respectively. This regeneration resulted in the restoration of agonist-induced excitatory contraction (82%) and neuron evoked relaxation (83%). The functional studies with specific neuronal nitric oxide (NO) synthase blocker confirmed that restoration of relaxation was NO mediated and neuronally derived. The simultaneous delivery of ICCs observed 35.7% higher neuronal differentiation and functional restoration compared with injection of NPCs alone. Injected NPCs and ICCs integrated into the dysfunctional ex vivo pylorus tissues and restored neuromuscular functionality. The co-transplantation of NPCs and ICCs can be used to treat neurodegenerative disorders of the pylorus.