Biology subjects

Powley, T. L.

Publications and source records attributed to Powley, T. L..

6 recordsLinked to original sources

bioRxiv2023

Mapping the Organization and Morphology of Calcitonin Gene-Related Peptide (CGRP)-IR Axons in the Whole Mouse Stomach

Nociceptive afferent axons innervate the stomach and send signals to the brain and spinal cord. Peripheral nociceptive afferents can be detected with a variety of markers [e.g., substance P (SP) and calcitonin gene-related peptide (CGRP)]. We recently examined the topographical organization and morphology of SP-immunoreactive (SP-IR) axons in the whole mouse stomach muscular layer. However, the distribution and morphological structure of CGRP-IR axons remain unclear. We used immunohistochemistry labeling and applied a combination of imaging techniques, including confocal and Zeiss Imager M2 microscopy, Neurolucida 360 tracing, and integration of axon tracing data into a 3D stomach scaffold to characterize CGRP-IR axons and terminals in the whole mouse stomach muscular layers. We found that: 1) CGRP-IR axons formed extensive terminal networks in both ventral and dorsal stomachs. 2) CGRP-IR axons densely innervated the blood vessels. 3) CGRP-IR axons ran in parallel with the longitudinal and circular muscles. Some axons ran at angles through the muscular layers. 4) They also formed varicose terminal contacts with individual myenteric ganglion neurons. 5) CGRP-IR occurred in DiI-labeled gastric-projecting neurons in the dorsal root and vagal nodose ganglia, indicating CGRP-IR axons were visceral afferent axons. 6) CGRP-IR axons did not colocalize with tyrosine hydroxylase (TH) or vesicular acetylcholine transporter (VAChT) axons in the stomach, indicating CGRP-IR axons were not visceral efferent axons. 7) CGRP-IR axons were traced and integrated into a 3D stomach scaffold. For the first time, we provided a topographical distribution map of CGRP-IR axon innervation of the whole stomach muscular layers at the cellular/axonal/varicosity scale.

neuroscience↗

bioRxiv2021

Neurons in the Nucleus Tractus Solitarius are Selective to the Orientation of Gastric Electrical Stimulation

Gastric electrical stimulation (GES) is a bioelectric intervention for gastroparesis, obesity, and other functional gastrointestinal disorders. In a potential mechanism of action, GES activates the nerve endings of vagal afferent neurons and induces the vago-vagal reflex through the nucleus tractus solitarius (NTS) in the brainstem. However, it is unclear where and how to stimulate in order to optimize the vagal afferent responses. To address this question with electrophysiology in rats, we applied mild electrical currents to two serosal targets on the distal forestomach with dense distributions of vagal intramuscular arrays that innervated the circular and longitudinal smooth muscle layers. During stimulation, we recorded single and multi-unit responses from gastric neurons in NTS and evaluated how the recorded responses depended on the stimulus orientation and amplitude. We found that NTS responses were highly selective to the stimulus orientation for a range of stimulus amplitudes. The strongest responses were observed when the applied current flowed in the same direction as the intramuscular arrays in parallel with the underlying smooth muscle fibers. Our results suggest that gastric neurons in NTS may encode the orientation-specific activity of gastric smooth muscles relayed by vagal afferent neurons. This finding suggests that the orientation of GES is critical to effective engagement of vagal afferents and should be considered in light of the structural phenotypes of vagal terminals in the stomach.

neuroscience↗

bioRxiv2021

Stomach serosal arteries distinguish gastric regions of the rat

Because the stomach in situ has few distinctive surface features and changes shape dramatically with food intake, we have used microCT imaging to (1) characterize the pattern of arteries, potential landmarks, on the stomach wall and (2) evaluate how meal-related shape changes affect the size of the different regions. The stomach receives its blood supply primarily from two pairs of vessels, the gastric and gastroepiploic arteries. Each of the three regions of the stomach is delineated by a distinctive combination of arterial fields: The corpus, consistent with its dynamic secretory activity and extensive mucosa, is supplied by extensive arterial trees formed by the left and right gastric arteries. These major arteries course circularly from the lesser towards the greater curvature, distally along both left and right walls of the corpus, and branch rostrally to supply the region. The muscular antrum is characterized by smaller arterial branches arising primarily from the right gastroepiploic artery that follows the distal greater curvature and secondarily from small, distally directed arteries supplied by the large vessels of the left and right gastric arteries. The forestomach, essentially devoid of mucosal tissue and separated from the corpus by the limiting ridge, is vascularized predominantly by a network of small arteries issued from the left gastroepiploic artery coursing around the proximal greater curvature, as well as from higher order and smaller branches issued by the gastric and celiac arteries. The regions of the stomach empty at different rates, thus changing the dimensions of the organ regions non-linearly.

physiology↗

bioRxiv2020

Automatic Assessment of Human Gastric Motility and Emptying from Dynamic 3D Magnetic Resonance Imaging

BackgroundTime-sequenced magnetic resonance imaging (MRI) of the stomach is an emerging technique for non-invasive assessment of gastric emptying and motility. However, an automated and systematic image processing pipeline for analyzing dynamic 3D (i.e., 4D) gastric MRI data is not yet available. This study introduces an MRI protocol for imaging the stomach with high spatiotemporal isotropic resolution and provides an integrated pipeline for assessing gastric emptying and motility simultaneously. MethodsDiet contrast-enhanced MRI images were acquired from seventeen healthy humans after they consumed a naturalistic contrast meal. An automated image processing pipeline was developed to correct for respiratory motion, to segment and compartmentalize the lumen-enhanced stomach, to quantify total gastric and compartmental emptying, and to compute and visualize gastric motility on the surface of the stomach. Key ResultsThe gastric segmentation reached an accuracy of 91.10{+/-}0.43% with the Type-I error and Type-II error being 0.11{+/-}0.01% and 0.22{+/-}0.01%, respectively. Gastric volume decreased 34.64{+/-}2.8% over 1 hour where the emptying followed a linear-exponential pattern. The gastric motility showed peristaltic patterns with a median = 4 wave-fronts (range 3 - 6) and a mean frequency of 3.09{+/-}0.07 cycles per minute (CPM). Further, the contractile amplitude was stronger in the antrum than in the corpus (antrum vs. corpus: 5.18{+/-}0.24 vs. 3.30{+/-}0.16 mm; p < .001). Conclusions & InferencesThe automated, streamlined software can process dynamic 3D MRI images and produce comprehensive and personalized profiles of gastric motility and emptying. This software will facilitate the application of MRI for monitoring gastric dynamics in research and clinical settings.

bioengineering↗

bioRxiv2018

Vagus Nerve Stimulation Promotes Gastric Emptying by Increasing Pyloric Opening Measured with Magnetic Resonance Imaging

BackgroundVagus nerve stimulation (VNS) is an emerging electroceutical therapy for remedying gastric disorders that are poorly managed by pharmacological treatments and/or dietary changes. Such therapy seems promising since the vagovagal neurocircuitry controlling the enteric nervous system strongly influences gastric functions.\n\nMethodsHere, the modulatory effects of left cervical VNS on gastric emptying in rats was quantified using a 1) feeding protocol in which the animal voluntarily consumed a post-fast, gadolinium-labeled meal and 2) newly developed, robust, sensitive and non-invasive imaging strategy to measure antral motility, pyloric activity and gastric emptying based on contrast-enhanced magnetic resonance imaging (MRI) and computer-assisted image processing pipelines.\n\nKey ResultsVNS significantly accelerated gastric emptying (control vs. VNS: 24.9{+/-}3.5% vs. 40.7{+/-}3.9% of meal emptied per 4hrs, p<0.05). This effect resulted from a greater relaxation of the pyloric sphincter (control vs. VNS: 1.4{+/-}0.2 vs. 2.5{+/-}0.5 mm2 cross-sectional area of lumen, p<0.05), without notable changes in antral contraction amplitude (control vs. VNS: 30.6{+/-}3.0% vs. 32.5{+/-}3.0% occlusion), peristaltic velocity (control vs. VNS: 0.67{+/-}0.03 vs. 0.67{+/-}0.03 mm/s), or frequency (control vs. VNS: 6.3{+/-}0.1 vs. 6.4{+/-}0.2 cpm). The degree to which VNS relaxed the pylorus positively correlated with gastric emptying rate (r = 0.5465, p<0.01).\n\nConclusions & InferencesThe MRI protocol employed in this study is expected to enable advanced preclinical studies to understand stomach pathophysiology and its therapeutics. Results from this study suggest an electroceutical treatment approach for gastric emptying disorders using cervical VNS to control the degree of pyloric sphincter relaxation.\n\nKey PointsO_LIVagus nerve stimulation is emerging as a new electroceutical therapy for treating gastric disorders. However, its underlying mechanism(s) and therapeutic effect(s) remain incompletely understood.\nC_LIO_LIVagus nerve stimulation significantly accelerated gastric emptying by promoting the relaxation of the pyloric sphincter.\nC_LIO_LIMRI offers high spatial and temporal resolution to non-invasively characterize gastric motility and physiology in preclinical animal models.\nC_LI

bioengineering↗

bioRxiv2017

Vagal Nerve Stimulation Triggers Wide-Spread Evoked Responses and Changes in Large-Scale Functional Connectivity in Rat Brains

Vagus nerve stimulation (VNS) is a therapy for epilepsy and depression. However, its efficacy varies and its mechanism remains unclear. Prior studies have used functional magnetic resonance imaging (fMRI) to map brain activations with VNS in human brains, but have reported inconsistent findings. The source of inconsistency is likely attributable to the complex temporal characteristics of VNS-evoked fMRI responses that cannot be fully explained by simplified response models in the conventional model-based analysis for activation mapping. To address this issue, we acquired 7-Tesla blood oxygenation level dependent fMRI data from anesthetized Sprague-Dawley rats receiving electrical stimulation at the left cervical vagus nerve. Using spatially independent component analysis, we identified 20 functional brain networks and detected the network-wise activations with VNS in a data-driven manner. Our results showed that VNS activated 15 out of 20 brain networks, and the activated regions covered >76% of the brain volume. The time course of the evoked response was complex and distinct across regions and networks. In addition, VNS altered the strengths and patterns of correlations among brain networks relative to those in the resting state. The most notable changes in network-network interactions were related to the limbic system. Together, such profound and widespread effects of VNS may underlie its unique potential for a wide range of therapeutics to relieve central or peripheral conditions.

neuroscience↗