Motility Recordings Research Articles

High‐Fat Diet Induced Modulation of Glutamatergic Currents in Neurons of the Dorsal Motor Nucleus of the Vagus Increases Gastric Tone and Motility

Understanding how vagally‐mediated neurocircuits are affected by alterations in diet is crucial to addressing dysregulated feeding behaviors and energy balance, as well as their role in the development of obesity. We have demonstrated previously that acute high fat diet (HFD) exposure modulates glutamatergic neurotransmission to vagal efferent motoneurons. The purpose of this study was to test the hypothesis that acute HFD increases activation of synaptic NMDA receptors (NMDA‐R) on gastric‐projecting dorsal motor nucleus of the vagus (DMV) neurons, which increases vagal efferent drive to the stomach.Sprague Dawley rats (4–8 weeks of age) of both sexes were fed a control diet (14% kcal from fat) throughout the study, or a HFD (60% kcal from fat) for 3–5 days prior to experimentation. Daily food intake was measured from singly‐housed rats for 4 days prior and throughout exposure to HFD. Whole cell patch clamp recordings of gastric‐projecting DMV neurons were made from thin (300μm) brainstem slices. The effects of the NMDA‐R antagonist, AP5 (25μM) on amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs) as well as action potential firing (AP) firing rate were examined. In vivo recordings of gastric motility and tone were made in response to microinjection of the non‐selective ionotropic glutamate antagonist, kynurenic acid (100pmol/60nL) and AP5 (500pmol/60nL).HFD exposure had no significant effect on caloric intake (control 55±4kcal/24hr vs acute HFD 59±9kcal/24hr; p>0.05) during the acute (3–5 day) period of study. After acute exposure to HFD, however, 9/15 DMV neurons responded to AP5 with a significant decrease in mEPSC amplitude and frequency (24.6±2.9pA vs 17.5±1.7pA; 1.4±0.3 pulses per second (p.p.s) vs 0.5±0.1p.p.s, respectively P<0.05 for each) as compared to only 1/18 control neurons. (18.7±1.3pA vs 18.0±1.3pA, P>0.05). In control conditions, AP5 had no effect on AP firing rate on 7/10 neurons (40.0±4.8 events/30sec vs 47.9±6.5 events/30sec, P>0.05), however, firing rate was decreased significantly in 5/5 neurons following acute HFD exposure (27.4±4.87 events/30sec vs 21.1±13.6 events/30sec, P<0.05). Brainstem microinjection of kynurenic acid had no effect on antral motility in control rats (102.5±17.6% of baseline, P>0.05), but significantly reduced motility following acute HFD exposure (59.9±1.10% of baseline, P<0.05).These data suggest that acute HFD exposure increases NMDA‐R activation, increases DMV neuronal excitability and, subsequently, vagal efferent control of gastric motility. Since this NMDA‐R activation is observed only during periods of caloric balance, these results suggest that plasticity within vagal neurocircuit glutamatergic signaling may be a critical homeostatic response to altered diet that helps maintain appropriate feeding behavior and caloric intake to defend against the development of obesity.Support or Funding InformationNSF IOS1148079 to Kirsteen BrowningThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Role of Central Orexin‐A in Restraint Stress‐induced Gastric Dysmotility in Rats

Stress exposure stimulates the production of corticotropin‐releasing factor (CRF) in hypothalamic paraventricular nucleus (PVN) which in turn influences gastrointestinal (GI) motor functions by altering autonomic outflow in brain. In rodents, acute restraint stress (ARS) has been shown to delay gastric emptying (GE) by impairing the postprandial coordination of of antro‐pyloric contractions through a CRF‐dependent pathway. Besides its well‐defined orexigenic function, the hypothalamic neuropeptide orexin‐A (OXA) is also known to alter GI motor functions through central autonomic pathways. OXA‐producing cells reside mainly in lateral hypothalamic area (LHA), while its receptor OX1R is found in PVN. Accumulating evidence indicate that OXA‐containing neurons send intra‐hypothalamic projections to the CRF‐producing cells in PVN. Furthermore, central administration of OXA has been shown to enhance CRF‐induced neuroendocrine functions suggesting that central OXA may contribute to the CRF‐mediated impairment of GI motor functions under stressed conditions. The aim of the present study was to investigate the involvement of orexin‐A in CRF‐induced gastric motor dysfunction under stressed conditions. Central (icv) drug administrations were performed through an injection cannula stereotaxically placed into the lateral ventricle. Solid GE was measured following an overnight fasting in non‐stressed (NS) and ARS‐loaded rats following central pretreatment of CRF and OXA antagonists α‐helical‐CRF9,41 (10 nmol, 5 μl) and SB‐334867 (100 nmol, 5 μl), respectively. For recording of gastric motility, two miniature strain gages were implanted onto the serosal surface of antrum and pylorus. Postprandial antro‐pyloric contractions were monitored in conscious and freely‐moving rats simultaneously with microdialysis. To perform microdialysis, a probe with high molecular cut‐off membrane was placed into the PVN. The intra‐PVN microinjection of vehicle or selective SB‐334867 (10 nmol, 100 nL) was performed prior to the perfusion of the probe with artificial cerebro‐spinal fluid (aCSF) containing high KCl (100 mmol/L). CRF concentrations in microdialysis samples were quantified by enzyme immunoassay. Compared with NS rats, ARS significantly (p<0.01) delayed GE. The ARS‐induced delayed GE was partially attenuated both by pretreatment of SB‐334867 (p<0.05) and α‐helical‐CRF9,41 (p<0.05), whereas it was completely restored (p<0.01) when both antagonists were administered together. Perfusion with high KCl‐containing aCSF significantly increased the CRF level in microdialysates which was significantly attenuated by intra‐PVN microinjection of SB‐334867. Perfusion of KCl impaired the coordination of postprandial antro‐pyloric contractions. Compared with vehicle‐injected rats, KCL‐induced alterations were remarkably abolished by SB‐334867. These results suggest that central OXA plays a role in stress‐induced alterations in gastric motor functions through OX1R. Therefore, OX1R antagonism appears to be a candidate for the treatment of the stress‐related gastric motor dysfunctions.

Computer vision-based diameter maps to study fluoroscopic recordings of small intestinal motility from conscious experimental animals.

When available, fluoroscopic recordings are a relatively cheap, non-invasive and technically straightforward way to study gastrointestinal motility. Spatiotemporal maps have been used to characterize motility of intestinal preparations in vitro, or in anesthetized animals in vivo. Here, a new automated computer-based method was used to construct spatiotemporal motility maps from fluoroscopic recordings obtained in conscious rats. Conscious, non-fasted, adult, male Wistar rats (n=8) received intragastric administration of barium contrast, and 1-2hours later, when several loops of the small intestine were well-defined, a 2minutes-fluoroscopic recording was obtained. Spatiotemporal diameter maps (Dmaps) were automatically calculated from the recordings. Three recordings were also manually analyzed for comparison. Frequency analysis was performed in order to calculate relevant motility parameters. In each conscious rat, a stable recording (17-20seconds) was analyzed. The Dmaps manually and automatically obtained from the same recording were comparable, but the automated process was faster and provided higher resolution. Two frequencies of motor activity dominated; lower frequency contractions (15.2±0.9cpm) had an amplitude approximately five times greater than higher frequency events (32.8±0.7cpm). The automated method developed here needed little investigator input, provided high-resolution results with short computing times, and automatically compensated for breathing and other small movements, allowing recordings to be made without anesthesia. Although slow and/or infrequent events could not be detected in the short recording periods analyzed to date (17-20seconds), this novel system enhances the analysis of in vivo motility in conscious animals.

Neurotensin Changes Propulsive Activity into a Segmental Motor Pattern in the Rat Colon.

Background/AimsNeurotensin is a gut-brain peptide with both inhibitory and excitatory actions on the colonic musculature; our objective was to understand the implications of this for motor patterns occurring in the intact colon of the rat.MethodsThe effects of neurotensin with concentrations ranging from 0.1–100 nM were studied in the intact rat colon in vitro, by investigating spatio-temporal maps created from video recordings of colonic motility before and after neurotensin.ResultsLow concentration of neurotensin (0.1–1 nM) inhibited propagating long distance contractions and rhythmic propagating motor complexes; in its place a slow propagating rhythmic segmental motor pattern developed. The neurotensin receptor 1 antagonist SR-48692 prevented the development of the segmental motor pattern. Higher concentrations of neurotensin (10 nM and 100 nM) were capable of restoring long distance contraction activity and inhibiting the segmental activity. The slow propagating segmental contraction showed a rhythmic contraction—relaxation cycle at the slow wave frequency originating from the interstitial cells of Cajal associated with the myenteric plexus pacemaker. High concentrations given without prior additions of low concentrations did not evoke the segmental motor pattern. These actions occurred when neurotensin was given in the bath solution or intraluminally. The segmental motor pattern evoked by neurotensin was inhibited by the neural conduction blocker lidocaine.ConclusionsNeurotensin (0.1–1 nM) inhibits the dominant propulsive motor patterns of the colon and a distinct motor pattern of rhythmic slow propagating segmental contractions develops. This motor pattern has the hallmarks of haustral boundary contractions.

966 High-Resolution Colonic Motility Recordings In Vivo Compared With Ex Vivo Recordings After Colectomy, in Patients With Slow Transit Constipation

966 High-Resolution Colonic Motility Recordings In Vivo Compared With Ex Vivo Recordings After Colectomy, in Patients With Slow Transit Constipation

The presence and role of interstitial cells of Cajal in the proximal intestine of shorthorn sculpin (Myoxocephalus scorpius).

Rhythmic contractions of the mammalian gastrointestinal tract can occur in the absence of neuronal or hormonal stimulation owing to the generation of spontaneous electrical activity by interstitial cells of Cajal (ICC) that are electrically coupled to smooth muscle cells. The myogenically driven component of gastrointestinal motility patterns in fish probably also involves ICC; however, little is known of their presence, distribution and function in any fish species. In the present study, we combined immunohistochemistry and in vivo recordings of intestinal motility to investigate the involvement of ICC in the motility of the proximal intestine in adult shorthorn sculpin (Myoxocephalus scorpius). Antibodies against anoctamin 1 (Ano1, a Ca2+-activated Cl- channel), revealed a dense network of multipolar, repeatedly branching cells in the myenteric region of the proximal intestine, similar in many regards to the mammalian ICC-MY network. The addition of benzbromarone, a potent blocker of Ano1, altered the motility patterns seen in vivo after neural blockade with TTX. The results indicate that ICC are integral for the generation and propagation of the majority of rhythmic contractile patterns in fish, although their frequency and amplitude can be modulated via neural activity.

Effect of Ethanol Exposure on Slow Wave Activity and Smooth Muscle Contraction in the Rat Small Intestine.

Ethanol ingestion causes a variety of gastrointestinal disturbances including motility alterations. Slow wave propagation coordinates gastrointestinal motility, and abnormal slow wave activity is thought to contribute to motility disorders. To date, however, little is known about the effect of acute ethanol on motility disturbances associated with slow wave activity. To investigate the effect of ethanol on small intestine slow wave activity. Segments (3-5 cm long) were isolated from the rat duodenum, jejunum, and ileum and mounted in an organ bath superfused with a normal Tyrode solution or with 1, 3, or 5% ethanol containing Tyrode. The electrical activities were recorded using an array of 121 extracellular electrodes, and motility recordings were performed using a digital video camera. The frequency and amplitude of slow wave activity were not altered at 1, 3, or 5% ethanol concentrations, but a significant drop in velocity was found at 3 and 5% ethanol. Furthermore, inexcitable areas appeared in a dose-dependent manner. Slow wave was sometimes also seen to propagate in a circular fashion, thereby describing a reentrant loop. Finally, in all duodenal, jejunal, and ileal segments, ethanol inhibited contractions and became fully quiescent at 3-5%. These studies for the first time demonstrate that ethanol significantly inhibits slow wave and spike activity in a dose-dependent manner and could also initiate reentrant activities. Intestinal contractions were also inhibited in a dose-dependent manner. In conclusion, ethanol inhibits both slow wave activity and motor activity to cause ethanol-induced intestinal disturbances.

New telemetry device for the measurement of gastrointestinal motility in rats and comparison with standard equipment.

To perform stress-free recording of gastrointestinal motility in rats with strain gauge transducers, telemetry equipment had to be developed. We developed, programmed, and tested a new telemetry device that records gastrointestinal motility in freely moving rats using strain gauge transducers. The device can collect and transmit data in freely moving rats. Data are received and stored for later analysis with a regular PC. Linear calibration curves were obtained for the strain gauge transducers used. We compared data obtained with the new telemetry device with data gathered with standard equipment and could not find any statistically significant difference. Wired gastric and colonic contraction frequencies were 4.6 ± 0.3 per minute and 1.5 ± 0.3 per minute, whereas telemetric contraction frequencies were 4.4 ± 0.1 per minute and 1.25 ± 0.1 per minute. The new telemetry device is a very useful tool for the measurement of gastrointestinal motility in rats.

Involvement of 5-HT3 and 5-HT4 receptors in colonic motor patterns in rats.

Colonic migrating motor complexes in the rat constitute two distinct propulsive motor patterns, pan-colonic rhythmic long distance contractions (LDCs), and rhythmic propulsive motor complexes (RPMCs) occurring primarily in the mid/distal colon. Interstitial cells of Cajal govern their rhythmicity, but their occurrence is dependent on neural programs. Our aim was to investigate the involvement of 5-HT3 and 5-HT4 receptors in the generation and pharmacological control of the motor patterns. Effects of 5-HT-related drugs on colonic motor patterns were analyzed through spatio-temporal maps created from video recordings of whole organ motility. 5-HT3 antagonists abolished RPMCs and LDCs. 5-HT4 agonists inhibited LDCs; they promoted RPMCs, which was blocked by the 5-HT4 antagonist GR 125487. 5-HT and the 5-HT3 agonist m-CPBG strongly inhibited LDCs and RPMCs. The generation of LDCs involves ongoing 5-HT release acting on 5-HT3 and 5-HT4 receptors. The spontaneous generation of RPMCs involves ongoing 5-HT release acting on 5-HT3 but not 5-HT4 receptors. Prucalopride and mosapride promote RPMCs, an effect that is inhibited by the 5-HT4 receptor antagonist GR 125487. A 5-HT3 agonist does not promote RPMCs. Segmentation, including a pattern of sequential segmental activity not previously described, can occur without significant involvement of 5-HT3 and 5-HT4 receptors. 5-HT and a 5-HT3 agonist are strongly inhibitory indicating that 5-HT receptors are present in inhibitory pathways which are normally not involved in the generation of spontaneous or distention-induced motor patterns.

Effect of entacapone on colon motility and ion transport in a rat model of Parkinson's disease.

To study the effects of entacapone, a catechol-O-methyltransferase inhibitor, on colon motility and electrolyte transport in Parkinson's disease (PD) rats. Distribution and expression of catechol-O-methyltransferase (COMT) were measured by immunohistochemistry and Western blotting methods. The colonic smooth muscle motility was examined in vitro by means of a muscle motility recording device. The mucosal electrolyte transport of PD rats was examined by using a short-circuit current (ISC ) technique and scanning ion-selective electrode technique (SIET). Intracellular detection of cAMP and cGMP was accomplished by radioimmunoassay testing. COMT was expressed in the colons of both normal and PD rats, mainly on the apical membranes of villi and crypts in the colon. Compared to normal controls, PD rats expressed less COMT. The COMT inhibitor entacapone inhibited contraction of the PD rat longitudinal muscle in a dose-dependent manner. The β2 adrenoceptor antagonist ICI-118,551 blocked this inhibitory effect by approximately 67% (P < 0.01). Entacapone increased mucosal ISC in the colon of rats with PD. This induction was significantly inhibited by apical application of Cl(-) channel blocker diphenylamine-2, 2'-dicarboxylic acid, basolateral application of Na(+)-K(+)-2Cl(-)co-transporter antagonist bumetanide, elimination of Cl(-) from the extracellular fluid, as well as pretreatment using adenylate cyclase inhibitor MDL12330A. As an inhibitor of prostaglandin synthetase, indomethacin can inhibit entacapone-induced ISC by 45% (P < 0.01). When SIET was applied to measure Cl(-) flux changes, this provided similar results. Entacapone significantly increased intracellular cAMP content in the colonic mucosa, which was greatly inhibited by indomethacin. COMT expression exists in rat colons. The β2 adrenoceptor is involved in the entacapone-induced inhibition of colon motility. Entacapone induces cAMP-dependent Cl(-) secretion in the PD rat.

Su1912 μ Opioid Receptor Activation Protects Against Intestinal Ischemia-Reperfusion Injury in Mice Through Different Pathways During Early and Late Phase of Reperfusion

Background: Neuropeptide S (NPS) is expressed by gastrointestinal (GI) enteroendocrine cells and macrophages in rat and man. Polymorphisms of the NPS receptor are linked to increased risk of inflammatory bowel disease as well as motor and sensory disturbances of the gut, suggesting a role for NPS in GI disorders. Further knowledge of NPS effects on motility and inflammation is needed. Methods: Studies of motility were carried out in rats with electrodes implanted in the small bowel. NPS was infused IV for 60 min and effects on myoelectrical activity were recorded. Motility effects of NPS were further studied as luminal pressure changes in anaesthetized rats where the proximal small intestine with intact blood supply was perfused with saline for motility recordings. Tissue samples were obtained from rats for evaluation of gene expression and protein elaboration of inflammatory biomarkers. Muscle strips of the human stomach, small intestine and colon were used for pharmacological analysis in organ baths of motility responses to NPS. Localization of the NPS receptor was done with fluorescent-protein tagging using Cy3-NPS. Plasma levels of NPS were measured using ELISA in 5 healthy and 14 IBD patients before and after meal. Results: In conscious rats, NPS 1 nmol kg-1min-1 increased irregular spiking, 4 nmol kg-1min-1 reduced spiking and increased the MMC cycle length (P=0.005). In anesthetized rats, NPS 0.01-1 nmol kg-1min-1 dose-dependently reduced small bowel motility (P<0.001). In rats, NPS also increased the mRNA expression of iNOS, and CXCL1 and IL-1β at the protein level. In human, fluorescent protein-tagging showed the NPS receptor primarily to be present in enolase-positive nerve fibers, but some scattered also in muscle tissue. In organ baths, NPS 1-100 nM caused TTX-dependent relaxations of the smooth muscle. We found no detectable levels of NPS in plasma of neither healthy subjects nor IBD patients. Conclusion: NPS has a smooth muscle-relaxing effect in the GI tract and dampens myoelectrical and contractile motor activity of the small bowel. This is achieved primarily through an inhibition of nerve-mediated relaxation of smooth muscle cells. Circulating NPS levels in humans are undetectable in healthy subjects and in active IBD. This implies that NPS exerts its inhibitory function by a paracrine or neurocrine mechanism in the gut. NPS seems also capable of intervening with inflammation by increasing gut cytokines and iNOS expression.

Su1911 Neuropeptide S: Effects on Motility, Contractility and Inflammation in the Rat and Human Gastrointestinal Tract

Background: Neuropeptide S (NPS) is expressed by gastrointestinal (GI) enteroendocrine cells and macrophages in rat and man. Polymorphisms of the NPS receptor are linked to increased risk of inflammatory bowel disease as well as motor and sensory disturbances of the gut, suggesting a role for NPS in GI disorders. Further knowledge of NPS effects on motility and inflammation is needed. Methods: Studies of motility were carried out in rats with electrodes implanted in the small bowel. NPS was infused IV for 60 min and effects on myoelectrical activity were recorded. Motility effects of NPS were further studied as luminal pressure changes in anaesthetized rats where the proximal small intestine with intact blood supply was perfused with saline for motility recordings. Tissue samples were obtained from rats for evaluation of gene expression and protein elaboration of inflammatory biomarkers. Muscle strips of the human stomach, small intestine and colon were used for pharmacological analysis in organ baths of motility responses to NPS. Localization of the NPS receptor was done with fluorescent-protein tagging using Cy3-NPS. Plasma levels of NPS were measured using ELISA in 5 healthy and 14 IBD patients before and after meal. Results: In conscious rats, NPS 1 nmol kg-1min-1 increased irregular spiking, 4 nmol kg-1min-1 reduced spiking and increased the MMC cycle length (P=0.005). In anesthetized rats, NPS 0.01-1 nmol kg-1min-1 dose-dependently reduced small bowel motility (P<0.001). In rats, NPS also increased the mRNA expression of iNOS, and CXCL1 and IL-1β at the protein level. In human, fluorescent protein-tagging showed the NPS receptor primarily to be present in enolase-positive nerve fibers, but some scattered also in muscle tissue. In organ baths, NPS 1-100 nM caused TTX-dependent relaxations of the smooth muscle. We found no detectable levels of NPS in plasma of neither healthy subjects nor IBD patients. Conclusion: NPS has a smooth muscle-relaxing effect in the GI tract and dampens myoelectrical and contractile motor activity of the small bowel. This is achieved primarily through an inhibition of nerve-mediated relaxation of smooth muscle cells. Circulating NPS levels in humans are undetectable in healthy subjects and in active IBD. This implies that NPS exerts its inhibitory function by a paracrine or neurocrine mechanism in the gut. NPS seems also capable of intervening with inflammation by increasing gut cytokines and iNOS expression.

Motility patterns of ex vivo intestine segments depend on perfusion mode.

To evaluate and characterize motility patterns from small intestinal gut segments depending on different perfusion media and pressures. Experiments were carried out in a custom designed perfusion chamber system to validate and standardise the perfusion technique used. The perfusion chamber was built with a transparent front wall allowing for optical motility recordings and a custom made fastener to hold the intestinal segments. Experiments with different perfusion and storage media combined with different luminal pressures were carried out to evaluate the effects on rat small intestine motility. Software tools which enable the visualization and characterization of intestinal motility in response to different stimuli were used to evaluate the videotaped experiments. The data collected was presented in so called heatmaps thus providing a concise overview of form and strength of contractility patterns. Furthermore, the effect of different storage media on tissue quality was evaluated. Haematoxylin-Eosin stainings were used to compare tissue quality depending on storage and perfusion mode. Intestinal motility is characterized by different repetitive motility patterns, depending on the actual situation of the gut. Different motility patterns could be recorded and characterized depending on the perfusion pressure and media used. We were able to describe at least three different repetitive patterns of intestinal motility in vitro. Patterns with an oral, anal and oro-anal propagation direction could be recorded. Each type of pattern finalized its movement with or without a subsequent distension of the wavefront. Motility patterns could clearly be distinguished in heatmap diagrams. Furthermore undirected motility could be observed. The quantity of the different patterns varies and is highly dependent on the perfusion medium used. Tissue preservation varies depending on the perfusion medium utilized, therefore media with a simple composition as Tyrode solution can only be recommended for short time experiments. The more complex media, MEM-HEPES medium and especially AQIX(®) RS-I tissue preservation reagent preserved the tissue much better during perfusion. Perfusion media have to be carefully chosen considering type and duration of the experiments. If excellent tissue quality is required, complex media are favorable. Perfusion pressure is also of great importance due to the fact that a minimum amount of luminal pressure seems to be necessary to trigger intestinal contractions.

Different computer-assisted sperm analysis (CASA) systems highly influence sperm motility parameters

In this study, we examined different computer-assisted sperm analysis (CASA) systems (CRISMAS, Hobson Sperm Tracker, and Image J CASA) on the exact same video recordings to evaluate the differences in sperm motility parameters related to the specific CASA used. To cover a wide range of sperm motility parameters, we chose 12-second video recordings at 25 and 50 Hz frame rates after sperm motility activation using three taxonomically distinct fish species (sterlet: Acipenser ruthenus L.; common carp: Cyprinus carpio L.; and rainbow trout: Oncorhynchus mykiss Walbaum) that are characterized by essential differences in sperm behavior during motility. Systematically higher values of velocity and beat cross frequency (BCF) were observed in video recordings obtained at 50 Hz frame frequency compared with 25 Hz for all three systems. Motility parameters were affected by the CASA and species used for analyses. Image J and CRISMAS calculated higher curvilinear velocity (VCL) values for rainbow trout and common carp at 25 Hz frequency compared with the Hobson Sperm Tracker, whereas at 50 Hz, a significant difference was observed only for rainbow trout sperm recordings. No significant difference was observed between the CASA systems for sterlet sperm motility at 25 and 50 Hz. Additional analysis of 1-second segments taken at three time points (1, 6, and 12 seconds of the recording) revealed a dramatic decrease in common carp and rainbow trout sperm speed. The motility parameters of sterlet spermatozoa did not change significantly during the 12-second motility period and should be considered as a suitable model for longer motility analyses. Our results indicated that the CASA used can affect motility results even when the same motility recordings are used. These results could be critically altered by the recording quality, time of analysis, and frame rate of camera, and could result in erroneous conclusions.

Tu1782 Weak Peristalsis With Large Breaks Is Associated With Higher Acid Exposure and Delayed Reflux Clearance in the Supine Position in GERD Patients

INTRODUCTION It has been demonstrated that among esophageal motor abnormalities, impaired peristalsis of the esophageal body may account for delayed bolus transit and impaired esophageal refl ux clearance in patients with complicated gastroesophageal refl ux disease (GERD) ( 1,2 ). In particular, several studies have shown that ineffective esophageal motility (IEM), defi ned as the presence of peristaltic waves at the distal esophagus with amplitude < 30 mm Hg and / or nontransmitted proximal contractions, is frequently observed in GERD patients; however, the functional relevance remains controversial ( 3 ). In GERD patients, increasing degrees of esophageal mucosal damage have been reported either to cause, or be the result of, severe worsening of esophageal function ( 4,5 ). Nevertheless, even if IEM has been associated with prolonged acid exposure time (AET) ( 6 ), it has been demonstrated that in GERD patients, only severe, but not mild IEM, is associated with prolonged clearance and AET, particularly when in the supine position ( 7 ). Th e recent development of high-resolution manometry (HRM) has led to an improvement of our knowledge regarding esophageal motility and is considered the gold standard in the study of esophageal motor disorders ( 8 ). Indeed, HRM combined with multichannel impedance (HRM-MI) monitoring allows simultaneous recording and analysis of the esophageal motility and of the bolus transit. Fox et al. ( 9 )demonstrated, using HRM coupled with videofl uoroscopy, that HRM pressure topography plots predict bolus transit more accurately than conventional manometry. Moreover, these authors reported that, as a consequence of the increased spatial resolution, HRM is also able to detect segmental breaks of the esophageal peristalsis that would otherwise have been missed with conventional manometry. More recently, Bulsiewicz et al. ( 10 ) showed in healthy subjects and in patients with nonobstructive dysphagia that peristaltic breaks of < 2 cm in the 20 mm Hg or < 3 cm in the 30 mm Hg isobaric contour are associated with complete bolus clearance, whereas larger breaks predict delayed bolus clearance. Moreover, it has been proposed that weak peristalsis could be defi ned Weak Peristalsis With Large Breaks Is Associated With Higher Acid Exposure and Delayed Refl ux Clearance in the Supine Position in GERD Patients

Neurogenic and Myogenic Properties of Pan-Colonic Motor Patterns and Their Spatiotemporal Organization in Rats

Background and AimsBetter understanding of intrinsic control mechanisms of colonic motility will lead to better treatment options for colonic dysmotility. The aim was to investigate neurogenic and myogenic control mechanisms underlying pan-colonic motor patterns.MethodsAnalysis of in vitro video recordings of whole rat colon motility was used to explore motor patterns and their spatiotemporal organizations and to identify mechanisms of neurogenic and myogenic control using pharmacological tools.ResultsStudy of the pan-colonic spatiotemporal organization of motor patterns revealed: fluid-induced or spontaneous rhythmic propulsive long distance contractions (LDCs, 0.4–1.5/min, involving the whole colon), rhythmic propulsive motor complexes (RPMCs) (0.8–2.5/min, dominant in distal colon), ripples (10–14/min, dominant in proximal colon), segmentation and retrograde contractions (0.1–0.8/min, prominent in distal and mid colon). Spontaneous rhythmic LDCs were the dominant pattern, blocked by tetrodotoxin, lidocaine or blockers of cholinergic, nitrergic or serotonergic pathways. Change from propulsion to segmentation and distal retrograde contractions was most prominent after blocking 5-HT3 receptors. In the presence of all neural blockers, bethanechol consistently evoked rhythmic LDC-like propulsive contractions in the same frequency range as the LDCs, indicating the existence of myogenic mechanisms of initiation and propulsion.ConclusionsNeurogenic and myogenic control systems orchestrate distinct and variable motor patterns at different regions of the pan-colon. Cholinergic, nitrergic and serotonergic pathways are essential for rhythmic LDCs to develop. Rhythmic motor patterns in presence of neural blockade indicate the involvement of myogenic control systems and suggest a role for the networks of interstitial cells of Cajal as pacemakers.

Dopamine enhances gastric motility through D1 dopaminergic receptors on cholinergic neurons in the myenteric plexus of rats

ObjectivesInvestigate the effect of dopamine on the gastric motility and the underlying mechanism.MethodsImmunofluorescence and gastric motility recording by organ bath study.ResultThe immunoreactivities of D1 and D2 were distributed in the choline acetyltransferase (ChAT)‐immunoreactive neurons in the myenteric plexus of rats. The gastric motility in vitro was enhanced from 8.2 to 10.8£g¡Ámin£©by DA in the concentrations of 1¡Á10–8mol/L (n=10, p&lt;0.05). However, DA manifested inhibitory role at the higher concentrations of 3¡Á10–6mol/L. The excitatory effect of DA was mimicked by SKF‐38393, a selective agonist of D1‐like receptors in dose‐dependent manner, and blocked by neuronal sodium channel blocker, tetrodotoxin (TTX) in 1¡Á10–5mol/L and atropine (competitive nonselective antagonist of muscarinic acetylcholine receptors) in 1¡Á10–5mol/L (n=8, p&lt;0.05). The selective D2‐like receptor antagonist sulpride and selective D2‐like agonist Quipirole did not affect both the excitatory and inhibitory effect of DA.ConclusionsThe present study demonstrates that dopamine is able to enhance gastric motility in lower concentration through D1 dopaminergic receptors activating acetylcholine release from myenteric nerve plexus. The higher dose of DA can inhibit gastric motility, but the mechanism needs to be further investigated.

Effects of acute temperature changes on gut physiology in two species of sculpin from the west coast of Greenland

For a fish to thrive, the gut must function efficiently. This is achieved through a range of processes, including controlled patterns of gut motility and modifications in gut blood flow. The knowledge of how gut functions in fish are affected by environmental temperature is sparse, and in order to understand how changes in climate may affect fish populations, we need to understand how gut blood flow and gut motility are affected by changes in temperature. By simultaneous recording of gut blood flow, gut motility, cardiac output, heart rate and cardiac stroke volume, in vivo at 4, 9 and 14 °C, the acute thermal sensitivity of a thermal generalist (shorthorn sculpin Myoxocephalu scorpius) was compared to the more strictly Arctic species (Arctic sculpin M. scorpioides). Temperature effects on gut motility were further explored in vitro, using isolated smooth muscles. Elevated water temperatures increased gut blood flow and contractile activity. Contraction frequency increased nearly threefold and gut blood flow almost doubled with the 10 °C increase. Both cardiac output and heart rate increased with temperature, while cardiac stroke volume decreased. The cholinergic agonist carbachol was most potent on smooth muscles at 9 °C. There were no differences between the two species, suggesting that the gastrointestinal and cardiovascular systems of Arctic sculpin, although a more pronounced Arctic species, have similar abilities to cope with acute fluctuations in water temperature as shorthorn sculpin. The impact of increased gut activity at higher temperatures needs further investigation before the effects of climate change can be predicted.

A pilot study with simultaneous recording of changes in motility and cortical electrical activity of rats during four weeks of oral manganese exposure

Manganese as an environmental neurotoxicant can cause oral exposure. Six rats were equipped with a connector “crown”, allowing repeated recording of electrocorticogram (ECoG) with simultaneous recording of motor activity in an open field box. Weekly one 30-min recording session was held, and after two control sessions, four of the six rats had 2.5 mg/ml manganese chloride in their drinking water. The treated rats showed higher motility during the exposure period than the untreated ones; and substantially decreased total ECoG power without marked change the spectrum. The changes of both motility and ECoG were correlated to the individual brain Mn levels, and the activity decrease during a session was correlated to the total ECoG power. These effects can be likened to early adult manganism and to symptoms of children exposed to Mn via drinking water. Repeated simultaneous recording of open field motility and spontaneous cortical activity seems suitable to detect early electrophysiological and behavioral effects of an oral neurotoxic exposure.

Heterogeneity in Esophageal Motility in Reflux Patients With Different Symptom Presentation: Studies With Combined Impedance and Manometry

peristalsis could be modulated by baclofen and mosapride. Methods: In all 15 healthy subjects (5 female, mean age 22, range 20-26 yr), secondary peristalsis was generated by slow and rapid mid-esophageal injections of air after a baseline recording of esophageal motility. Three separate sessions with 40 mg oral baclofen, 40 mg oral mosapride or placebo were randomly performed to test their effects on esophageal secondary peristalsis with at least a 1-week interval. Results: Baclofen significantly increased the threshold volume for triggering secondary peristalsis during slow air distension (P = 0.003) and rapid air distension (P = 0.002). Baclofen significantly reduced the rate of secondary peristalsis by rapid air distension from 90% to 30% (P = 0.0002). Despite increasing basal LES pressure (P = 0.03), baclofen did not affect any of peristaltic parameters by primary or secondary peristalsis. Mosapride significantly decreased the threshold volume for triggering secondary peristalsis during rapid air distension (P = 0.04). Secondary peristalsis was triggered more frequently in response to rapid air distension after application of mosapride (P = 0.02). Mosapride significantly increased pressure wave amplitudes of secondary peristalsis during slow (P = 0.001) and rapid air distension (P = 0.002). Conclusions: Inhibition of baclofen on the triggering of secondary peristalsis presents during esophageal distension, indicating that sensory part of secondary peristalsis is probably mediated by the GABAB receptors. However, baclofen does not lead to any motility change in secondary peristalsis as induced by either slow or rapid air distension. Mosapride appears to enhance sensitivity to distension-induced secondary peristalsis and facilitates secondary peristaltic contractility, suggesting the involvement of 5-HT4 in the modulation of esophageal secondary peristalsis in humans.