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Article ; Online: Brain-gut communication: vagovagal reflexes interconnect the two "brains".

Powley, Terry L

American journal of physiology. Gastrointestinal and liver physiology

2021 Volume 321, Issue 5, Page(s) G576–G587

Abstract: The gastrointestinal tract has its own "brain," the enteric nervous system or ENS, that executes routine housekeeping functions of digestion. The dorsal vagal complex in the central nervous system (CNS) brainstem, however, organizes vagovagal reflexes ... ...

Abstract	The gastrointestinal tract has its own "brain," the enteric nervous system or ENS, that executes routine housekeeping functions of digestion. The dorsal vagal complex in the central nervous system (CNS) brainstem, however, organizes vagovagal reflexes and establishes interconnections between the entire neuroaxis of the CNS and the gut. Thus, the dorsal vagal complex links the "CNS brain" to the "ENS brain." This brain-gut connectome provides reflex adjustments that optimize digestion and assimilation of nutrients and fluid. Vagovagal circuitry also generates the plasticity and adaptability needed to maintain homeostasis to coordinate among organs and to react to environmental situations. Arguably, this dynamic flexibility provided by the vagal circuitry may, in some circumstances, lead to or complicate maladaptive disorders.
MeSH term(s)	Animals ; Brain/physiology ; Enteric Nervous System/physiology ; Gastrointestinal Tract/innervation ; Humans ; Neuronal Plasticity ; Reflex ; Vagus Nerve/physiology
Language	English
Publishing date	2021-10-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	603840-2
ISSN	1522-1547 ; 0193-1857
ISSN (online)	1522-1547
ISSN	0193-1857
DOI	10.1152/ajpgi.00214.2021
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Article ; Online: A flexible, thin-film microchannel electrode array device for selective subdiaphragmatic vagus nerve recording.

Lim, Jongcheon / Zoss, Peter A / Powley, Terry L / Lee, Hyowon / Ward, Matthew P

Microsystems & nanoengineering

2024 Volume 10, Page(s) 16

Abstract: The vagus nerve (VN) plays an important role in regulating physiological conditions in the gastrointestinal (GI) tract by communicating via the parasympathetic pathway to the enteric nervous system (ENS). However, the lack of knowledge in the ... ...

Abstract	The vagus nerve (VN) plays an important role in regulating physiological conditions in the gastrointestinal (GI) tract by communicating via the parasympathetic pathway to the enteric nervous system (ENS). However, the lack of knowledge in the neurophysiology of the VN and GI tract limits the development of advanced treatments for autonomic dysfunctions related to the VN. To better understand the complicated underlying mechanisms of the VN-GI tract neurophysiology, it is necessary to use an advanced device enabled by microfabrication technologies. Among several candidates including intraneural probe array and extraneural cuff electrodes, microchannel electrode array devices can be used to interface with smaller numbers of nerve fibers by securing them in the separate channel structures. Previous microchannel electrode array devices to interface teased nerve structures are relatively bulky with thickness around 200 µm. The thick design can potentially harm the delicate tissue structures, including the nerve itself. In this paper, we present a flexible thin film based microchannel electrode array device (thickness: 11.5 µm) that can interface with one of the subdiaphragmatic nerve branches of the VN in a rat. We demonstrated recording evoked compound action potentials (ECAP) from a transected nerve ending that has multiple nerve fibers. Moreover, our analysis confirmed that the signals are from C-fibers that are critical in regulating autonomic neurophysiology in the GI tract.
Language	English
Publishing date	2024-01-23
Publishing country	England
Document type	Journal Article
ISSN	2055-7434
ISSN (online)	2055-7434
DOI	10.1038/s41378-023-00637-6
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Article ; Online: Stomach serosal arteries distinguish gastric regions of the rat.

Jaffey, Deborah M / Chesney, Logan / Powley, Terry L

Journal of anatomy

2021 Volume 239, Issue 4, Page(s) 903–912

Abstract: Because the stomach in situ has few distinctive surface features and changes shape dramatically with food intake, we have used micro-CT imaging combined with two distinct contrast agents to (1) characterize the pattern of arteries, potential landmarks, ... ...

Abstract	Because the stomach in situ has few distinctive surface features and changes shape dramatically with food intake, we have used micro-CT imaging combined with two distinct contrast agents 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. Images generated with a contrast agent injected directly into the heart during perfusion enabled a thorough look at the organizational features of the stomach angioarchitecture. 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, travelling, respectively, on the ventral and dorsal stomach surfaces. These major arteries course circularly from the lesser towards the greater curvature, distally along both left (or ventral) and right (or dorsal) 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. These distinctive arterial fields appear to distinguish the major gastric regions, irrespective of the degree of fill of the stomach. Volume assessments of stomach compartments were made from images of iodine-stained stomachs. By varying the delay time between eating and perfusion, we were able to probe the emptying behavior of the stomach and demonstrate that the regions of the stomach empty at different rates, thus changing the relative dimensions of the organ regions. Notably, and despite these shape changes, the gastric arteries appear to form a regular, particularly recognizable, and lateralized pattern corresponding to the corpus that should be of use in guiding surgical and experimental interventions.
MeSH term(s)	Animals ; Arteries ; Gastric Artery ; Rats ; Stomach/diagnostic imaging
Language	English
Publishing date	2021-06-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2955-5
ISSN	1469-7580 ; 0021-8782
ISSN (online)	1469-7580
ISSN	0021-8782
DOI	10.1111/joa.13480
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Article ; Online: Gastric neurons in the nucleus tractus solitarius are selective to the orientation of gastric electrical stimulation.

Cao, Jiayue / Wang, Xiaokai / Powley, Terry L / Liu, Zhongming

Journal of neural engineering

2021 Volume 18, Issue 5

Abstract: Objective. ...

Abstract	Objective.
MeSH term(s)	Animals ; Electric Stimulation ; Neurons ; Rats ; Solitary Nucleus ; Stomach ; Vagus Nerve
Language	English
Publishing date	2021-10-26
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2170901-4
ISSN	1741-2552 ; 1741-2560
ISSN (online)	1741-2552
ISSN	1741-2560
DOI	10.1088/1741-2552/ac2ec6
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Article ; Online: Fractal Microelectrodes for More Energy-Efficient Cervical Vagus Nerve Stimulation.

Lim, Jongcheon / Eiber, Calvin D / Sun, Anina / Maples, Amanda / Powley, Terry L / Ward, Matthew P / Lee, Hyowon

Advanced healthcare materials

2023 Volume 12, Issue 19, Page(s) e2202619

Abstract: Vagus nerve stimulation (VNS) has the potential to treat various peripheral dysfunctions, but the traditional cuff electrodes for VNS are susceptible to off-target effects. Microelectrodes may enable highly selective VNS that can mitigate off-target ... ...

Abstract	Vagus nerve stimulation (VNS) has the potential to treat various peripheral dysfunctions, but the traditional cuff electrodes for VNS are susceptible to off-target effects. Microelectrodes may enable highly selective VNS that can mitigate off-target effects, but they suffer from the increased impedance. Recent studies on microelectrodes with non-Euclidean geometries have reported higher energy efficiency in neural stimulation applications. These previous studies use electrodes with mm/cm-scale dimensions, mostly targeted for myelinated fibers. This study evaluates fractal microelectrodes for VNS in a rodent model (N = 3). A thin-film device with fractal and circle microelectrodes is fabricated to compare their neural stimulation performance on the same radial coordinate of the nerve. The results show that fractal microelectrodes can activate C-fibers with up to 52% less energy (p = 0.012) compared to circle microelectrodes. To the best of the knowledge, this work is the first to demonstrate a geometric advantage of fractal microelectrodes for VNS in vivo.
MeSH term(s)	Vagus Nerve Stimulation/methods ; Microelectrodes ; Fractals ; Vagus Nerve/physiology
Language	English
Publishing date	2023-04-23
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2649576-4
ISSN	2192-2659 ; 2192-2640
ISSN (online)	2192-2659
ISSN	2192-2640
DOI	10.1002/adhm.202202619
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Article ; Online: Acute effects of vagus nerve stimulation parameters on gastric motility assessed with magnetic resonance imaging.

Lu, Kun-Han / Cao, Jiayue / Phillips, Robert / Powley, Terry L / Liu, Zhongming

Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society

2020 Volume 32, Issue 7, Page(s) e13853

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Action Potentials ; Afferent Pathways/physiology ; Animals ; Duodenum/innervation ; Duodenum/physiology ; Efferent Pathways/physiology ; Gastrointestinal Motility ; Magnetic Resonance Imaging ; Male ; Pyloric Antrum/innervation ; Pyloric Antrum/physiology ; Pylorus/innervation ; Pylorus/physiology ; Rats, Sprague-Dawley ; Vagus Nerve/physiology ; Vagus Nerve Stimulation/methods
Language	English
Publishing date	2020-04-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1186328-6
ISSN	1365-2982 ; 1350-1925
ISSN (online)	1365-2982
ISSN	1350-1925
DOI	10.1111/nmo.13853
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Article: A novel statistical methodology for quantifying the spatial arrangements of axons in peripheral nerves.

Shemonti, Abida Sanjana / Plebani, Emanuele / Biscola, Natalia P / Jaffey, Deborah M / Havton, Leif A / Keast, Janet R / Pothen, Alex / Dundar, M Murat / Powley, Terry L / Rajwa, Bartek

Frontiers in neuroscience

2023 Volume 17, Page(s) 1072779

Abstract: A thorough understanding of the neuroanatomy of peripheral nerves is required for a better insight into their function and the development of neuromodulation tools and strategies. In biophysical modeling, it is commonly assumed that the complex spatial ... ...

Abstract	A thorough understanding of the neuroanatomy of peripheral nerves is required for a better insight into their function and the development of neuromodulation tools and strategies. In biophysical modeling, it is commonly assumed that the complex spatial arrangement of myelinated and unmyelinated axons in peripheral nerves is random, however, in reality the axonal organization is inhomogeneous and anisotropic. Present quantitative neuroanatomy methods analyze peripheral nerves in terms of the number of axons and the morphometric characteristics of the axons, such as area and diameter. In this study, we employed spatial statistics and point process models to describe the spatial arrangement of axons and Sinkhorn distances to compute the similarities between these arrangements (in terms of first- and second-order statistics) in various vagus and pelvic nerve cross-sections. We utilized high-resolution transmission electron microscopy (TEM) images that have been segmented using a custom-built high-throughput deep learning system based on a highly modified U-Net architecture. Our findings show a novel and innovative approach to quantifying similarities between spatial point patterns using metrics derived from the solution to the optimal transport problem. We also present a generalizable pipeline for quantitative analysis of peripheral nerve architecture. Our data demonstrate differences between male- and female-originating samples and similarities between the pelvic and abdominal vagus nerves.
Language	English
Publishing date	2023-03-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2023.1072779
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Article ; Online: Spinal afferent innervation in flat-mounts of the rat stomach: anterograde tracing.

Ma, Jichao / Nguyen, Duyen / Madas, Jazune / Kwiat, Andrew M / Toledo, Zulema / Bizanti, Ariege / Kogut, Nicole / Mistareehi, Anas / Bendowski, Kohlton / Zhang, Yuanyuan / Chen, Jin / Li, De-Pei / Powley, Terry L / Furness, John B / Cheng, Zixi

Scientific reports

2023 Volume 13, Issue 1, Page(s) 17675

Abstract: The dorsal root ganglia (DRG) project spinal afferent axons to the stomach. However, the distribution and morphology of spinal afferent axons in the stomach have not been well characterized. In this study, we used a combination of state-of-the-art ... ...

Abstract	The dorsal root ganglia (DRG) project spinal afferent axons to the stomach. However, the distribution and morphology of spinal afferent axons in the stomach have not been well characterized. In this study, we used a combination of state-of-the-art techniques, including anterograde tracer injection into the left DRG T7-T11, avidin-biotin and Cuprolinic Blue labeling, Zeiss M2 Imager, and Neurolucida to characterize spinal afferent axons in flat-mounts of the whole rat stomach muscular wall. We found that spinal afferent axons innervated all regions with a variety of distinct terminal structures innervating different gastric targets: (1) The ganglionic type: some axons formed varicose contacts with individual neurons within myenteric ganglia. (2) The muscle type: most axons ran in parallel with the longitudinal and circular muscles and expressed spherical varicosities. Complex terminal structures were observed within the circular muscle layer. (3) The ganglia-muscle mixed type: some individual varicose axons innervated both myenteric neurons and the circular muscle, exhibiting polymorphic terminal structures. (4) The vascular type: individual varicose axons ran along the blood vessels and occasionally traversed the vessel wall. This work provides a foundation for future topographical anatomical and functional mapping of spinal afferent axon innervation of the stomach under normal and pathophysiological conditions.
MeSH term(s)	Rats ; Animals ; Stomach/innervation ; Neurons ; Axons ; Muscles ; Ganglia, Spinal/anatomy & histology
Language	English
Publishing date	2023-10-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-43120-y
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Article ; Online: Automatic assessment of human gastric motility and emptying from dynamic 3D magnetic resonance imaging.

Lu, Kun-Han / Liu, Zhongming / Jaffey, Deborah / Wo, John M / Mosier, Kristine M / Cao, Jiayue / Wang, Xiaokai / Powley, Terry L

Neurogastroenterology and motility

2021 Volume 34, Issue 1, Page(s) e14239

Abstract: Background: Time-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 (ie, ...

Abstract	Background: Time-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 (ie, 4D) gastric MRI data has not been established. This study uses an MRI protocol for imaging the stomach with high spatiotemporal resolution and provides a pipeline for assessing gastric emptying and motility. Methods: Diet 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 luminal surface of the stomach. Key results: The 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 h 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. 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 < 0.001). Conclusions & inferences: Our analysis pipeline can process dynamic 3D MRI images and produce personalized profiles of gastric motility and emptying. It will facilitate the application of MRI for monitoring gastric dynamics in research and clinical settings.
MeSH term(s)	Adult ; Digestion/physiology ; Female ; Gastric Emptying/physiology ; Gastrointestinal Motility/physiology ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Stomach/diagnostic imaging ; Stomach/physiology ; Young Adult
Language	English
Publishing date	2021-08-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1186328-6
ISSN	1365-2982 ; 1350-1925
ISSN (online)	1365-2982
ISSN	1350-1925
DOI	10.1111/nmo.14239
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Article ; Online: Macrophages associated with the intrinsic and extrinsic autonomic innervation of the rat gastrointestinal tract.

Phillips, Robert J / Powley, Terry L

Autonomic neuroscience : basic & clinical

2012 Volume 169, Issue 1, Page(s) 12–27

Abstract: Interactions between macrophages and the autonomic innervation of gastrointestinal (GI) tract smooth muscle have received little experimental attention. To better understand this relationship, immunohistochemistry was performed on GI whole mounts from ... ...

Abstract	Interactions between macrophages and the autonomic innervation of gastrointestinal (GI) tract smooth muscle have received little experimental attention. To better understand this relationship, immunohistochemistry was performed on GI whole mounts from rats at three ages. The phenotypes, morphologies, and distributions of gut macrophages are consistent with the cells performing extensive housekeeping functions in the smooth muscle layers. Specifically, a dense population of macrophages was located throughout the muscle wall where they were distributed among the muscle fibers and along the vasculature. Macrophages were also associated with ganglia and connectives of the myenteric plexus and with the sympathetic innervation. Additionally, these cells were in tight registration with the dendrites and axons of the myenteric neurons as well as the varicosities along the length of the sympathetic axons, suggestive of a contribution by the macrophages to the homeostasis of both synapses and contacts between the various elements of the enteric circuitry. Similarly, macrophages were involved in the presumed elimination of neuropathies as indicated by their association with dystrophic neurons and neurites which are located throughout the myenteric plexus and smooth muscle wall of aged rats. Importantly, the patterns of macrophage-neuron interactions in the gut paralleled the much more extensively characterized interactions of macrophages (i.e., microglia) and neurons in the CNS. The present observations in the PNS as well as extrapolations from homologous microglia in the CNS suggest that GI macrophages play significant roles in maintaining the nervous system of the gut in the face of wear and tear, disease, and aging.
MeSH term(s)	Aging ; Animals ; Antigens, Differentiation/metabolism ; Autonomic Nervous System/cytology ; Autonomic Nervous System/metabolism ; Autonomic Nervous System/physiology ; Cell Aggregation ; Central Nervous System/cytology ; Central Nervous System/metabolism ; Central Nervous System/physiology ; Gastrointestinal Tract/cytology ; Gastrointestinal Tract/immunology ; Gastrointestinal Tract/innervation ; Gastrointestinal Tract/metabolism ; Homeostasis ; Macrophages/cytology ; Macrophages/immunology ; Macrophages/metabolism ; Male ; Microglia/cytology ; Microglia/immunology ; Microglia/metabolism ; Muscle, Smooth/cytology ; Muscle, Smooth/immunology ; Muscle, Smooth/innervation ; Muscle, Smooth/metabolism ; Myenteric Plexus/cytology ; Myenteric Plexus/immunology ; Myenteric Plexus/metabolism ; Neuroanatomical Tract-Tracing Techniques ; Neurons/cytology ; Neurons/immunology ; Neurons/metabolism ; Peripheral Nervous System/cytology ; Peripheral Nervous System/metabolism ; Peripheral Nervous System/physiology ; Rats ; Rats, Inbred BN ; Rats, Inbred F344 ; alpha-Synuclein/metabolism
Chemical Substances	Antigens, Differentiation ; Snca protein, rat ; alpha-Synuclein
Language	English
Publishing date	2012-03-20
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2020105-9
ISSN	1872-7484 ; 1566-0702
ISSN (online)	1872-7484
ISSN	1566-0702
DOI	10.1016/j.autneu.2012.02.004
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