Vagus nerve stimulation in bursts can efficiently modulate gastric contractions and contraction frequency at varying gastric pressures.

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.

CNS sites controlling the gastric pyloric sphincter: Neuroanatomical and functional study in the rat.

The pyloric sphincter receives parasympathetic vagal innervation from the dorsal motor nucleus of the vagus (DMV). However, little is known about its higher-order neurons and the nuclei that engage the DMV neurons controlling the pylorus. The purpose of the present study was twofold. First, to identify neuroanatomical connections between higher-order neurons and the DMV. This was carried out by using the transneuronal pseudorabies virus PRV-152 injected into rat pylorus torus and examining the brains of these animals for PRV labeling. Second, to identify the specific sites within the DMV that functionally control the motility and tone of the pyloric sphincter. For these studies, experiments were performed to assess the effect of DMV stimulation on pylorus activity in urethane-anesthetized male rats. A strain gauge force transducer was sutured onto the pyloric tonus to monitor tone and motility. L-glutamate (500 pmol/30 nL) was microinjected unilaterally into the rostral and caudal areas of the DMV. Data from the first study indicated that neurons labeled with PRV occurred in the DMV, hindbrain raphe nuclei, midbrain Edinger-Westphal nucleus, ventral tegmental area, lateral habenula, and arcuate nucleus. Data from the second study indicated that microinjected L-glutamate into the rostral DMV results in contraction of the pylorus blocked by intravenously administered atropine and ipsilateral vagotomy. L-glutamate injected into the caudal DMV relaxed the pylorus. This response was abolished by ipsilateral vagotomy but not by intravenously administered atropine or L-NG-nitroarginine methyl ester (L-NAME). These findings identify the anatomical and functional brain neurocircuitry involved in controlling the pyloric sphincter. Our results also show that site-specific stimulation of the DMV can differentially influence the activity of the pyloric sphincter by separate vagal nerve pathways.

Topographical distribution and morphology of SP-IR axons in the antrum, pylorus, and duodenum of mice.

Substance-P (SP) is a commonly used marker of nociceptive afferent axons, and it plays an important role in a variety of physiological functions including the regulation of motility, gut secretion, and vascular flow. Previously, we found that SP-immunoreactive (SP-IR) axons densely innervated the pyloric antrum of the flat-mount of the mouse whole stomach muscular layer. However, the regional distribution and morphology of SP-IR axons in the submucosa and mucosa were not well documented. In this study, the mouse antrum-pylorus-duodenum (APD) were transversely and longitudinally sectioned. A Zeiss M2 imager was used to scan the serial sections of each APD (each section montage consisted of 50-100 all-in-focus maximal projection images). To determine the detailed structures of SP-IR axons and terminals, we used the confocal microscope to scan the regions of interest. We found that 1) SP-IR axons innervated the muscular, submucosal, and mucosal layers. 2) In the muscular layer, SP-IR varicose axons densely innervated the muscles and formed varicose terminals which encircled myenteric neurons. 3) In the submucosa, SP-IR axons innervated blood vessels and submucosal ganglia and formed a network in Brunner's glands. 4) In the mucosa, SP-IR axons innervated the muscularis mucosae. Some SP-IR axons entered the lamina propria. 5) The muscular layer of the antrum and duodenum showed a higher SP-IR axon density than the pyloric sphincter. 6) SP-IR axons were from extrinsic and intrinsic origins. This work provided a comprehensive view of the distribution and morphology of SP-IR axons in the APD at single cell/axon/varicosity scale. This data will be used to create a 3D scaffold of the SP-IR axon innervation of the APD.

Gastroparesis.

Gastroparesis is characterized by symptoms suggestive of, and objective evidence of, delayed gastric emptying in the absence of mechanical obstruction. This review addresses the normal emptying of solids and liquids from the stomach and details the myogenic and neuromuscular control mechanisms, including the specialized function of the pyloric sphincter, that result in normal emptying, based predominantly on animal research. A clear understanding of fundamental mechanisms is necessary to comprehend derangements leading to gastroparesis, and additional research on human gastric muscles is needed. The section on pathophysiology of gastroparesis considers neuromuscular diseases that affect nonsphincteric gastric muscle, disorders of the extrinsic neural control, and pyloric dysfunction that lead to gastroparesis. The potential cellular basis for gastroparesis is attributed to the effects of oxidative stress and inflammation, with increased pro-inflammatory and decreased resident macrophages, as observed in full-thickness biopsies from patients with gastroparesis. Predominant diagnostic tests involving measurements of gastric emptying, the use of a functional luminal imaging probe, and high-resolution antral duodenal manometry in characterizing the abnormal motor functions at the gastroduodenal junction are discussed. Management is based on supporting nutrition; dietary interventions, including the physical reduction in particle size of solid foods; pharmacological agents, including prokinetics and anti-emetics; and interventions such as gastric electrical stimulation and pyloromyotomy. These are discussed briefly, and comment is added on the potential for individualized treatments in the future, based on optimal gastric emptying measurement and objective documentation of the underlying pathophysiology causing the gastroparesis.

Acute effects of vagus nerve stimulation parameters on gastric motility assessed with magnetic resonance imaging.

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.

Opioid-Induced Foregut Dysfunction.

The impact of opioid use on the lower gastrointestinal tract is well described, but recent opioid crisis has caused increased awareness of the detrimental effects of these drugs on esophageal and gastroduodenal motility. Opioid use has been associated with increased incidence of spastic esophageal motility disorders and gastroduodenal dysfunction. Opioid receptors are present with high abundance in the myenteric and submucosal plexus of the enteric nervous system. Activation of these receptors leads to suppressed excitability of the inhibitory musculomotor neurons and unchecked tonic contraction of the autogenic musculature (such as the lower esophageal sphincter and the pylorus).

The differential contribution of pacemaker neurons to synaptic transmission in the pyloric network of the Jonah crab, Cancer borealis.

Many neurons receive synchronous input from heterogeneous presynaptic neurons with distinct properties. An instructive example is the crustacean stomatogastric pyloric circuit pacemaker group, consisting of the anterior burster (AB) and pyloric dilator (PD) neurons, which are active synchronously and exert a combined synaptic action on most pyloric follower neurons. Previous studies in lobster have indicated that AB is glutamatergic, whereas PD is cholinergic. However, although the stomatogastric system of the crab Cancer borealis has become a preferred system for exploration of cellular and synaptic basis of circuit dynamics, the pacemaker synaptic output has not been carefully analyzed in this species. We examined the synaptic properties of these neurons using a combination of single-cell mRNA analysis, electrophysiology, and pharmacology. The crab PD neuron expresses high levels of choline acetyltransferase and the vesicular acetylcholine transporter mRNAs, hallmarks of cholinergic neurons. In contrast, the AB neuron expresses neither cholinergic marker but expresses high levels of vesicular glutamate transporter mRNA, consistent with a glutamatergic phenotype. Notably, in the combined synapses to follower neurons, 70-75% of the total current was blocked by putative glutamatergic blockers, but short-term synaptic plasticity remained unchanged, and although the total pacemaker current in two follower neuron types was different, this difference did not contribute to the phasing of the follower neurons. These findings provide a guide for similar explorations of heterogeneous synaptic connections in other systems and a baseline in this system for the exploration of the differential influence of neuromodulators.NEW & NOTEWORTHY The pacemaker-driven pyloric circuit of the Jonah crab stomatogastric nervous system is a well-studied model system for exploring circuit dynamics and neuromodulation, yet the understanding of the synaptic properties of the two pacemaker neuron types is based on older analyses in other species. We use single-cell PCR and electrophysiology to explore the neurotransmitters used by the pacemaker neurons and their distinct contribution to the combined synaptic potentials.

Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson's Disease.

Analysis of human pathology led Braak to postulate that α-synuclein (α-syn) pathology could spread from the gut to brain via the vagus nerve. Here, we test this postulate by assessing α-synucleinopathy in the brain in a novel gut-to-brain α-syn transmission mouse model, where pathological α-syn preformed fibrils were injected into the duodenal and pyloric muscularis layer. Spread of pathologic α-syn in brain, as assessed by phosphorylation of serine 129 of α-syn, was observed first in the dorsal motor nucleus, then in caudal portions of the hindbrain, including the locus coeruleus, and much later in basolateral amygdala, dorsal raphe nucleus, and the substantia nigra pars compacta. Moreover, loss of dopaminergic neurons and motor and non-motor symptoms were observed in a similar temporal manner. Truncal vagotomy and α-syn deficiency prevented the gut-to-brain spread of α-synucleinopathy and associated neurodegeneration and behavioral deficits. This study supports the Braak hypothesis in the etiology of idiopathic Parkinson's disease (PD).

Short-term synaptic dynamics control the activity phase of neurons in an oscillatory network.

In oscillatory systems, neuronal activity phase is often independent of network frequency. Such phase maintenance requires adjustment of synaptic input with network frequency, a relationship that we explored using the crab, Cancer borealis, pyloric network. The burst phase of pyloric neurons is relatively constant despite a > two fold variation in network frequency. We used noise input to characterize how input shape influences burst delay of a pyloric neuron, and then used dynamic clamp to examine how burst phase depends on the period, amplitude, duration, and shape of rhythmic synaptic input. Phase constancy across a range of periods required a proportional increase of synaptic duration with period. However, phase maintenance was also promoted by an increase of amplitude and peak phase of synaptic input with period. Mathematical analysis shows how short-term synaptic plasticity can coordinately change amplitude and peak phase to maximize the range of periods over which phase constancy is achieved.

Enteric nervous system in the European beaver (Castor fiber) pylorus - an immunohistochemical study.

European beaver (Castor fiber), the largest rodent species inhabiting a wide area of Eurasia, feeds mainly on dry parts of plants, bark or wood. Such kind of nourishment needs to be properly digested in each part of the gastrointestinal tract. The time of stomach digestion, which directly influences all the following steps of the digestion process, is precisely controlled by the pylorus and its innervation. However, virtually no data is available on the organization of the enteric nervous system in most of the wild animal species, including beavers. On the other hand, a pecu- liar diet consumed by beavers, suggests that the arrangement of their stomach intramural nerve elements can be atypical. Therefore, the present study investigated the distribution and chemical coding of neurons and nerve fibers in the pylorus of the European beaver. The experiment was performed on stomachs obtained from a group of 6 beavers caught in Northeastern region of Poland (due to beaver overpopulation). Pyloric wall tissue cryosections were double immunostained with a mixture of antibodies against pan-neuronal marker PGP 9.5 (to visualize enteric neurons) and ChAT (cholinergic marker), nNOS (nitrergic marker), SP, CGRP, Gal (peptidergic markers). Confocal microscopy analysis revealed that the majority of enteric nerve cells were clustered forming submucosal and myenteric ganglia and all the studied substances were expressed (in various amounts) in these neurons. We conclude, that the anatomical arrangement and chemical coding of intramural nerve elements in the beaver pylorus resemble those found in other mammalian species.

Similarities and differences in circuit responses to applied Gly1-SIFamide and peptidergic (Gly1-SIFamide) neuron stimulation.

Microcircuit modulation by peptides is well established, but the cellular/synaptic mechanisms whereby identified neurons with identified peptide transmitters modulate microcircuits remain unknown for most systems. Here, we describe the distribution of GYRKPPFNGSIFamide (Gly1-SIFamide) immunoreactivity (Gly1-SIFamide-IR) in the stomatogastric nervous system (STNS) of the crab Cancer borealis and the Gly1-SIFamide actions on the two feeding-related circuits in the stomatogastric ganglion (STG). Gly1-SIFamide-IR localized to somata in the paired commissural ganglia (CoGs), two axons in the nerves connecting each CoG with the STG, and the CoG and STG neuropil. We identified one Gly1-SIFamide-IR projection neuron innervating the STG as the previously identified modulatory commissural neuron 5 (MCN5). Brief (~10 s) MCN5 stimulation excites some pyloric circuit neurons. We now find that bath applying Gly1-SIFamide to the isolated STG also enhanced pyloric rhythm activity and activated an imperfectly coordinated gastric mill rhythm that included unusually prolonged bursts in two circuit neurons [inferior cardiac (IC), lateral posterior gastric (LPG)]. Furthermore, longer duration (>30 s) MCN5 stimulation activated a Gly1-SIFamide-like gastric mill rhythm, including prolonged IC and LPG bursting. The prolonged LPG bursting decreased the coincidence of its activity with neurons to which it is electrically coupled. We also identified local circuit feedback onto the MCN5 axon terminals, which may contribute to some distinctions between the responses to MCN5 stimulation and Gly1-SIFamide application. Thus, MCN5 adds to the few identified projection neurons that modulate a well-defined circuit at least partly via an identified neuropeptide transmitter and provides an opportunity to study peptide regulation of electrical coupled neurons in a functional context. NEW & NOTEWORTHY Limited insight exists regarding how identified peptidergic neurons modulate microcircuits. We show that the modulatory projection neuron modulatory commissural neuron 5 (MCN5) is peptidergic, containing Gly1-SIFamide. MCN5 and Gly1-SIFamide elicit similar output from two well-defined motor circuits. Their distinct actions may result partly from circuit feedback onto the MCN5 axon terminals. Their similar actions include eliciting divergent activity patterns in normally coactive, electrically coupled neurons, providing an opportunity to examine peptide modulation of electrically coupled neurons in a functional context.

Two central pattern generators from the crab, Cancer borealis, respond robustly and differentially to extreme extracellular pH.

The activity of neuronal circuits depends on the properties of the constituent neurons and their underlying synaptic and intrinsic currents. We describe the effects of extreme changes in extracellular pH - from pH 5.5 to 10.4 - on two central pattern generating networks, the stomatogastric and cardiac ganglia of the crab, Cancer borealis. Given that the physiological properties of ion channels are known to be sensitive to pH within the range tested, it is surprising that these rhythms generally remained robust from pH 6.1 to pH 8.8. The pH sensitivity of these rhythms was highly variable between animals and, unexpectedly, between ganglia. Animal-to-animal variability was likely a consequence of similar network performance arising from variable sets of underlying conductances. Together, these results illustrate the potential difficulty in generalizing the effects of environmental perturbation across circuits, even within the same animal.

Preservation of the celiac branch of the vagal nerve for pylorus-preserving gastrectomy: is it meaningful?

BACKGROUND: Preserving the hepatic and pyloric branches of the vagal nerve in laparoscopic pylorus-preserving gastrectomy (LPPG) is considered necessary to maintain the function of the pyloric cuff. However, the clinical benefits of preservation of the celiac branch of the vagal nerve (CBVN) remain unclear. METHODS: Of 391 patients who underwent LPPG for early gastric cancer, 116 patients in whom the CBVN was preserved (CBP group) and 58 patients in whom it was not preserved (non-CBP group) were selected through the propensity score-matching method. To evaluate the surgical and oncological safety of preserving the CBVN, postoperative morbidity and mortality were analyzed between these matched groups. Postoperative nutritional status, body weight changes, endoscopic findings, and the incidence of gallstones were compared to evaluate any functional advantages. RESULTS: The short-term surgical outcomes in the CBP group were similar to those in the non-CBP group. The number of dissected lymph nodes did not differ (34 vs. 33.5, P = 0.457), and the 5-year recurrence-free survival rates were also similar between both groups (99.1% vs. 97.1%, P = 0.844). There were no significant differences in postoperative nutritional status, body weight changes, or the incidence of gallstones. By endoscopy, 1 year after surgery residual food was frequently observed in both groups; however, there were no significant differences in the frequency of remnant gastritis and esophageal and bile reflux. CONCLUSIONS: Preserving CBVN in LPPG for early gastric cancer is a feasible procedure. However, no clinical benefits of the preservation of the CBVN after LPPG are identified.

[Value of endoscopy application in the management of complications after radical gastrectomy for gastric cancer].

Endoscopy plays an important role in the diagnosis and treatment of postoperative complications of gastric cancer. Endoscopic intervention can avoid the second operation and has attracted wide attention. Early gastric anastomotic bleeding after gastrectomy is the most common. With the development of technology, emergency endoscopy and endoscopic hemostasis provide a new treatment approach. According to the specific circumstances, endoscopists can choose metal clamp to stop bleeding, electrocoagulation hemostasis, local injection of epinephrine or sclerotherapy agents, and spraying specific hemostatic agents. Anastomotic fistula is a serious postoperative complication. In addition to endoscopically placing the small intestine nutrition tube for early enteral nutrition support treatment, endoscopic treatment, including stent, metal clip, OTSC, and Over-stitch suture system, can be chosen to close fistula. For anastomotic obstruction or stricture, endoscopic balloon or probe expansion and stent placement can be chosen. For esophageal anastomotic intractable obstruction after gastroesophageal surgery, radial incision of obstruction by the hook knife or IT knife, a new method named ERI, is a good choice. Bile leakage caused by bile duct injury can be treated by placing the stent or nasal bile duct. In addition, endoscopic methods are widely used as follows: abdominal abscess can be treated by the direct intervention under endoscopy; adhesive ileus can be treated by placing the catheter under the guidance of endoscopy to attract pressure; alkaline reflux gastritis can be rapidly diagnosed by endoscopy; gastric outlet obstruction mainly caused by cancer recurrence can be relieved by metal stent placement and the combination of endoscopy and X-ray can increase success rate; pyloric dysfunction and spasm caused by the vagus nerve injury during proximal gastrectomy can be treated by endoscopic pyloromyotomy, a new method named G-POEM, and the short-term outcomes are significant. Endoscopic submucosal dissection (ESD) allows complete resection of residual gastric precancerous lesions, however it should be performed by the experienced endoscopists.

Neurochemical Plasticity of the Coeliac-Superior Mesenteric Ganglion Complex Neurons Projecting to the Prepyloric Area of the Porcine Stomach following Hyperacidity.

This study was designed to determine neurochemical properties of the coeliac-superior mesenteric ganglion (CSMG) neurons supplying the prepyloric area of the porcine stomach in physiological state and following experimentally induced hyperacidity. To localize sympathetic neurons innervating the studied area of stomach, the neuronal retrograde tracer Fast Blue (FB) was applied to control animals and hydrochloric acid infusion (HCl) groups. After 23 days, animals of the HCl group were reintroduced into a state of general anesthesia and intragastrically given 5 mL/kg of body weight of 0.25 M aqueous solution of hydrochloric acid. On the 28th day, all animals were sacrificed. The CSMG complexes were then collected and processed for double-labeling immunofluorescence. In the control animals, FB-positive perikarya displayed immunoreactivity to tyrosine hydroxylase (TH), dopamine ß-hydroxylase (DßH), neuropeptide Y (NPY), and galanin (GAL). Experimentally induced gastric hyperacidity changed the neurochemical phenotype of the studied neurons. An upregulated expression of GAL and NPY and the de novo synthesis of neuronal nitric oxide synthase (nNOS) and leu5-enkephalin (LENK) as well as downregulated expression of TH and DßH in the stomach-projecting neurons were observed. These findings enrich existing knowledge about the participation of these active substances in adaptive mechanism(s) of the sympathetic neurons during pathological processes within the gastrointestinal tract.

Neuropeptide profile changes in sensory neurones after partial prepyloric resection in pigs.

This report details the first identification of the sources of sensory innervation of the porcine stomach prepyloric region. The Fast Blue (FB) retrograde tracing technique detected the sensory prepyloric neurons in the bilateral nodose ganglia (NGs) as well as thoracic dorsal root ganglia (DRGs). Double-labelling immunofluorescence demonstrated expression of substance P (SP), calcitonin gene-related peptide (CGRP), neuronal isoform of nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP) and galanin (GAL) in both NGs and DRGs. Additionally, we found that partial resection of the stomach prepyloric area increased expression of the SP, CGRP, NOS, VIP and GAL in the prepyloric sensory neurons. In the control left NGs, both a higher total number of FB-positive perikarya as well as a higher percentage of the peptides expressing prepyloric neurons were visualized than in the right NGs. However, compared to the control group, prepyloric resection evoked greater increases in peptide expression in the right-side NGs sensory neurons. In the ganglia of this side, the proportion of the SP-IR perikarya increased by approximately 15%, while CGRP-IR increased by 28%, NOS-IR 14%, VIP-IR 43% and GAL-IR 13%. On the opposite left side, the ganglia proportion of the CGRP-IR perikarya increased by approximately 10%, while NOS-IR increased by 3%, VIP-IR 36% and GAL-IR by 2%. The only decrease (by 5%) was observed in the case of SP expression. We also found that 92% of the sensory neurons originated from NGs and 8% from DRGs. Our results indicate that, in the pig, SP, CGRP, NOS, VIP and GAL participate in the vagal sensory transduction from the stomach prepyloric area. Moreover, increased expression of the peptides and neuronal isoform of nitric oxide synthase in the sensory neurons following transection of their peripheral dendrites suggests their possible participation in the neuronal recovery and/or reinnervation process.

The Influence of Gastric Antral Ulcerations on the Expression of Galanin and GalR1, GalR2, GalR3 Receptors in the Pylorus with Regard to Gastric Intrinsic Innervation of the Pyloric Sphincter.

Gastric antrum ulcerations are common disorders occurring in humans and animals. Such localization of ulcers disturbs the gastric emptying process, which is precisely controlled by the pylorus. Galanin (Gal) and its receptors are commonly accepted to participate in the regulation of inflammatory processes and neuronal plasticity. Their role in the regulation of gastrointestinal motility is also widely described. However, there is lack of data considering antral ulcerations in relation to changes in the expression of Gal and GalR1, GalR2, GalR3 receptors in the pyloric wall tissue and galaninergic intramural innervation of the pylorus. Two groups of pigs were used in the study: healthy gilts and gilts with experimentally induced antral ulcers. By double immunocytochemistry percentages of myenteric and submucosal neurons expressing Gal-immunoreactivity were determined in the pyloric wall tissue and in the population of gastric descending neurons supplying the pyloric sphincter (labelled by retrograde Fast Blue neuronal tracer). The percentage of Gal-immunoreactive neurons increased only in the myenteric plexus of the pyloric wall (from 16.14±2.06% in control to 25.5±2.07% in experimental animals), while no significant differences in other neuronal populations were observed between animals of both groups. Real-Time PCR revealed the increased expression of mRNA encoding Gal and GalR1 receptor in the pyloric wall tissue of the experimental animals, while the expression(s) of GalR2 and GalR3 were not significantly changed. The results obtained suggest the involvement of Gal, GalR1 and galaninergic pyloric myenteric neurons in the response of pyloric wall structures to antral ulcerations.

Role of Ih in differentiating the dynamics of the gastric and pyloric neurons in the stomatogastric ganglion of the lobster, Homarus americanus.

The hyperpolarization-activated inward cationic current (Ih) is known to regulate the rhythmicity, excitability, and synaptic transmission in heart cells and many types of neurons across a variety of species, including some pyloric and gastric mill neurons in the stomatogastric ganglion (STG) in Cancer borealis and Panulirus interruptus However, little is known about the role of Ih in regulating the gastric mill dynamics and its contribution to the dynamical bifurcation of the gastric mill and pyloric networks. We investigated the role of Ih in the rhythmic activity and cellular excitability of both the gastric mill neurons (medial gastric, gastric mill) and pyloric neurons (pyloric dilator, lateral pyloric) in Homarus americanus Through testing the burst period between 5 and 50 mM CsCl, and elimination of postinhibitory rebound and voltage sag, we found that 30 mM CsCl can sufficiently block Ih in both the pyloric and gastric mill neurons. Our results show that Ih maintains the excitability of both the pyloric and gastric mill neurons. However, Ih regulates slow oscillations of the pyloric and gastric mill neurons differently. Specifically, blocking Ih diminishes the difference between the pyloric and gastric mill burst periods by increasing the pyloric burst period and decreasing the gastric mill burst period. Moreover, the phase-plane analysis shows that blocking Ih causes the trajectory of slow oscillations of the gastric mill neurons to change toward the pyloric sinusoidal-like trajectories. In addition to regulating the pyloric rhythm, we found that Ih is also essential for the gastric mill rhythms and differentially regulates these two dynamics.

Incorporating spike-rate adaptation into a rate code in mathematical and biological neurons.

For a slowly varying stimulus, the simplest relationship between a neuron's input and output is a rate code, in which the spike rate is a unique function of the stimulus at that instant. In the case of spike-rate adaptation, there is no unique relationship between input and output, because the spike rate at any time depends both on the instantaneous stimulus and on prior spiking (the "history"). To improve the decoding of spike trains produced by neurons that show spike-rate adaptation, we developed a simple scheme that incorporates "history" into a rate code. We utilized this rate-history code successfully to decode spike trains produced by 1) mathematical models of a neuron in which the mechanism for adaptation (IAHP) is specified, and 2) the gastropyloric receptor (GPR2), a stretch-sensitive neuron in the stomatogastric nervous system of the crab Cancer borealis, that exhibits long-lasting adaptation of unknown origin. Moreover, when we modified the spike rate either mathematically in a model system or by applying neuromodulatory agents to the experimental system, we found that changes in the rate-history code could be related to the biophysical mechanisms responsible for altering the spiking.