scholarly journals Circuit-specific enteric glia regulate intestinal motor neurocircuits

2021 ◽  
Vol 118 (40) ◽  
pp. e2025938118
Author(s):  
Mohammad M. Ahmadzai ◽  
Luisa Seguella ◽  
Brian D. Gulbransen
Keyword(s):  
Nervous System ◽  
Purinergic Signaling ◽  
Proximal Colon ◽  
Enteric Neurons ◽  
Neural Pathways ◽  
Dependent Manner ◽  
Descending Pathways ◽  
Enteric Glia ◽  
Cholinergic Signaling ◽  
Peripheral Glia

Glia in the central nervous system exert precise spatial and temporal regulation over neural circuitry on a synapse-specific basis, but it is unclear if peripheral glia share this exquisite capacity to sense and modulate circuit activity. In the enteric nervous system (ENS), glia control gastrointestinal motility through bidirectional communication with surrounding neurons. We combined glial chemogenetics with genetically encoded calcium indicators expressed in enteric neurons and glia to study network-level activity in the intact myenteric plexus of the proximal colon. Stimulation of neural fiber tracts projecting in aboral, oral, and circumferential directions activated distinct populations of enteric glia. The majority of glia responded to both oral and aboral stimulation and circumferential pathways, while smaller subpopulations were activated only by ascending and descending pathways. Cholinergic signaling functionally specifies glia to the descending circuitry, and this network plays an important role in repressing the activity of descending neural pathways, with some degree of cross-inhibition imposed upon the ascending pathway. Glial recruitment by purinergic signaling functions to enhance activity within ascending circuit pathways and constrain activity within descending networks. Pharmacological manipulation of glial purinergic and cholinergic signaling differentially altered neuronal responses in these circuits in a sex-dependent manner. Collectively, our findings establish that the balance between purinergic and cholinergic signaling may differentially control specific circuit activity through selective signaling between networks of enteric neurons and glia. Thus, enteric glia regulate the ENS circuitry in a network-specific manner, providing profound insights into the functional breadth and versatility of peripheral glia.

scholarly journals Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways

2020 ◽  
Author(s):  
Lihua Ye ◽  
Munhyung Bae ◽  
Chelsi D. Cassilly ◽  
Sairam V. Jabba ◽  
Daniel W. Thorpe ◽  
...  
Keyword(s):  
Nervous System ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Enteroendocrine Cells ◽  
Enteric Neurons ◽  
Edwardsiella Tarda ◽  
Dependent Manner ◽  
Tryptophan Catabolism ◽  
Transient Receptor

SUMMARYThe intestinal epithelium senses nutritional and microbial stimuli using epithelial sensory enteroendocrine cells (EECs). EECs can communicate nutritional information to the nervous system, but similar mechanisms for microbial information are unknown. Using in vivo real-time measurements of EEC and nervous system activity in zebrafish, we discovered that the bacteria Edwardsiella tarda specifically activates EECs through the receptor transient receptor potential ankyrin A1 (Trpa1) and increases intestinal motility in an EEC-dependent manner. Microbial, pharmacological, or optogenetic activation of Trpa1+EECs directly stimulates vagal sensory ganglia and activates cholinergic enteric neurons through 5-HT. We identified a subset of indole derivatives of tryptophan catabolism produced by E. tarda and other gut microbes that potently activates zebrafish EEC Trpa1 signaling and also directly stimulates human and mouse Trpa1 and intestinal 5-HT secretion. These results establish a molecular pathway by which EECs regulate enteric and vagal neuronal pathways in response to specific microbial signals.

scholarly journals Neuronal programming by microbiota enables environmental regulation of intestinal motility

2019 ◽  
Author(s):  
Yuuki Obata ◽  
Stefan Boeing ◽  
Álvaro Castaño ◽  
Ana Carina Bon-Frauches ◽  
Mercedes Gomez de Agüero ◽  
...  
Keyword(s):  
Nervous System ◽  
Synaptic Activity ◽  
Enteric Neurons ◽  
Neural Pathways ◽  
Environmental Sensors ◽  
Environmental Signals ◽  
Distal Intestine ◽  
Aryl Hydrocarbon ◽  
System Output ◽  
Novel Strategy

AbstractEnvironmental signals modulate the activity of the nervous system and harmonize its output with the outside world. Synaptic activity is crucial for integrating sensory and effector neural pathways but the role of transcriptional mechanisms as environmental sensors in the nervous system remains unclear. By combining a novel strategy for transcriptomic profiling of enteric neurons with microbiota manipulation, we demonstrate that the transcriptional programs of intestinal neural circuits depend on their anatomical and physiological context. We also identify the ligand-dependent transcription factor Aryl hydrocarbon Receptor (AhR) is an intrinsic regulator of enteric nervous system output. AhR is instated as a neuronal biosensor in response to microbiota colonization allowing resident enteric neurons to directly monitor and respond to the intestinal microenvironment. We suggest that AhR signaling integrates neuronal activity with host defence mechanisms towards gut homeostasis and health.One Sentence SummaryMicrobiota induce expression of AhR in enteric neurons of the distal intestine enabling them to respond to environmental signals.

scholarly journals Development, Diversity, and Neurogenic Capacity of Enteric Glia

2022 ◽  
Vol 9 ◽  
Author(s):  
Werend Boesmans ◽  
Amelia Nash ◽  
Kinga R. Tasnády ◽  
Wendy Yang ◽  
Lincon A. Stamp ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Glial Cells ◽  
Cell Types ◽  
Vital Role ◽  
Enteric Neurons ◽  
Enteric Glia ◽  
Enteric Glial Cells ◽  
Functional Versatility

Enteric glia are a fascinating population of cells. Initially identified in the gut wall as the “support” cells of the enteric nervous system, studies over the past 20 years have unveiled a vast array of functions carried out by enteric glia. They mediate enteric nervous system signalling and play a vital role in the local regulation of gut functions. Enteric glial cells interact with other gastrointestinal cell types such as those of the epithelium and immune system to preserve homeostasis, and are perceptive to luminal content. Their functional versatility and phenotypic heterogeneity are mirrored by an extensive level of plasticity, illustrated by their reactivity in conditions associated with enteric nervous system dysfunction and disease. As one of the hallmarks of their plasticity and extending their operative relationship with enteric neurons, enteric glia also display neurogenic potential. In this review, we focus on the development of enteric glial cells, and the mechanisms behind their heterogeneity in the adult gut. In addition, we discuss what is currently known about the role of enteric glia as neural precursors in the enteric nervous system.

scholarly journals Cholinergic activation of enteric glia is a physiological mechanism that contributes to the regulation of gastrointestinal motility

2018 ◽  
Vol 315 (4) ◽  
pp. G473-G483 ◽  
Author(s):  
Ninotchska M. Delvalle ◽  
David E. Fried ◽  
Gretchen Rivera-Lopez ◽  
Luke Gaudette ◽  
Brian D. Gulbransen
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Muscarinic Receptors ◽  
Gastrointestinal Motility ◽  
Physiological Mechanism ◽  
Receptor Activation ◽  
Glial Activation ◽  
Enteric Neurons ◽  
Enteric Glia ◽  
Physiological Regulation

The reflexive activities of the gastrointestinal tract are regulated, in part, by precise interactions between neurons and glia in the enteric nervous system (ENS). Intraganglionic enteric glia are a unique type of peripheral glia that surround enteric neurons and regulate neuronal function, activity, and survival. Enteric glia express numerous neurotransmitter receptors that allow them to sense neuronal activity, but it is not clear if enteric glia monitor acetylcholine (ACh), the primary excitatory neurotransmitter in the ENS. Here, we tested the hypothesis that enteric glia detect ACh and that glial activation by ACh contributes to the physiological regulation of gut functions. Our results show that myenteric enteric glia express both the M3 and M5 subtypes of muscarinic receptors (MRs) and that muscarine drives intracellular calcium (Ca2+) signaling predominantly through M3R activation. To elucidate the functional effects of activation of glial M3Rs, we used GFAP::hM3Dq mice that express a modified human M3R (hM3Dq) exclusively on glial fibrillary acidic protein (GFAP) positive glia to directly activate glial hM3Dqs using clozapine- N-oxide. Using spatiotemporal mapping analysis, we found that the activation of glial hM3Dq receptors enhances motility reflexes ex vivo. Continuous stimulation of hM3Dq receptors in vivo, drove changes in gastrointestinal motility without affecting neuronal survival in the ENS and glial muscarinic receptor activation did not alter neuron survival in vitro. Our results provide the first evidence that GFAP intraganglionic enteric glia express functional muscarinic receptors and suggest that the activation of glial muscarinic receptors contributes to the physiological regulation of functions. NEW & NOTEWORTHY Enteric glia are emerging as novel regulators of enteric reflex circuits, but little is still known regarding the effects of specific transmitter pathways on glia and the resulting consequences on enteric reflexes. Here, we provide the first evidence that enteric glia monitor acetylcholine in the enteric nervous system and that glial activation by acetylcholine is a physiological mechanism that contributes to the functional regulation of intestinal reflexes.

Interleukin-1β activates specific populations of enteric neurons and enteric glia in the guinea pig ileum and colon

2003 ◽  
Vol 285 (6) ◽  
pp. G1268-G1276 ◽  
Author(s):  
Eric T. T. L. Tjwa ◽  
Joelle M. Bradley ◽  
Catherine M. Keenan ◽  
Alfons B. A. Kroese ◽  
Keith A. Sharkey
Keyword(s):  
Guinea Pig ◽  
Proinflammatory Cytokine ◽  
Enteric Neurons ◽  
Interleukin 1Β ◽  
Neural Pathways ◽  
Guinea Pig Ileum ◽  
Double Labeling ◽  
Enteric Glia ◽  
Cox 2 ◽  
Fos Expression

Fos expression was used to assess whether the proinflammatory cytokine interleukin-1β (IL-1β) activated specific, chemically coded neuronal populations in isolated preparations of guinea pig ileum and colon. Whether the effects of IL-1β were mediated through a prostaglandin pathway and whether IL-1β induced the expression of cyclooxygenase (COX)-2 was also examined. Single- and double-labeling immunohistochemistry was used after treatment of isolated tissues with IL-1β (0.1-10 ng/ml). IL-1β induced Fos expression in enteric neurons and also in enteric glia in the ileum and colon. For enteric neurons, activation was concentration-dependent and sensitive to indomethacin, in both the myenteric and submucosal plexuses in both regions of the gut. The maximum proportion of activated neurons differed between the ileal (∼15%) and colonic (∼42%) myenteric and ileal (∼60%) and colonic (∼75%) submucosal plexuses. The majority of neurons activated in the myenteric plexus of the ileum expressed nitric oxide synthase (NOS) or enkephalin immunoreactivity. In the colon, activated myenteric neurons expressed NOS. In the submucosal plexus of both regions of the gut, the majority of activated neurons were vasoactive intestinal polypeptide (VIP) immunoreactive. After treatment with IL-1β, COX-2 immunoreactivity was detected in the wall of the gut in both neurons and nonneuronal cells. In conclusion, we have found that the proinflammatory cytokine IL-1β specifically activates certain neurochemically defined neural pathways and that these changes may lead to disturbances in motility observed in the inflamed bowel.

Purinergic signaling in nervous system health and disease: Focus on pannexin 1

2021 ◽  
pp. 107840
Author(s):  
Juan C. Sanchez-Arias ◽  
Emma van der Slagt ◽  
Haley A. Vecchiarelli ◽  
Rebecca C. Candlish ◽  
Nicole York ◽  
...  
Keyword(s):  
Nervous System ◽  
Purinergic Signaling ◽  
Pannexin 1 ◽  
Health And Disease ◽  
Disease Focus

scholarly journals Long range synchronization within the enteric nervous system underlies propulsion along the large intestine in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Nick J. Spencer ◽  
Lee Travis ◽  
Lukasz Wiklendt ◽  
Marcello Costa ◽  
Timothy J. Hibberd ◽  
...  
Keyword(s):  
Nervous System ◽  
Smooth Muscle ◽  
Enteric Nervous System ◽  
Lymphatic Vessels ◽  
Distal Colon ◽  
Distal Region ◽  
Proximal Colon ◽  
Synchronous Firing ◽  
Electrophysiological Recordings ◽  
Intrinsic Neurons

AbstractHow the Enteric Nervous System (ENS) coordinates propulsion of content along the gastrointestinal (GI)-tract has been a major unresolved issue. We reveal a mechanism that explains how ENS activity underlies propulsion of content along the colon. We used a recently developed high-resolution video imaging approach with concurrent electrophysiological recordings from smooth muscle, during fluid propulsion. Recordings showed pulsatile firing of excitatory and inhibitory neuromuscular inputs not only in proximal colon, but also distal colon, long before the propagating contraction invades the distal region. During propulsion, wavelet analysis revealed increased coherence at ~2 Hz over large distances between the proximal and distal regions. Therefore, during propulsion, synchronous firing of descending inhibitory nerve pathways over long ranges aborally acts to suppress smooth muscle from contracting, counteracting the excitatory nerve pathways over this same region of colon. This delays muscle contraction downstream, ahead of the advancing contraction. The mechanism identified is more complex than expected and vastly different from fluid propulsion along other hollow smooth muscle organs; like lymphatic vessels, portal vein, or ureters, that evolved without intrinsic neurons.

Inhibitory control of proximal colonic motility by the sympathetic nervous system

1987 ◽  
Vol 253 (4) ◽  
pp. G531-G539 ◽  
Author(s):  
R. A. Gillis ◽  
J. Dias Souza ◽  
K. A. Hicks ◽  
A. W. Mangel ◽  
F. D. Pagani ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Nerve Stimulation ◽  
Adrenergic Receptors ◽  
Vagal Stimulation ◽  
Colonic Motility ◽  
Inhibitory Effect ◽  
Proximal Colon ◽  
Pelvic Nerve ◽  
Sympathetic Nervous

The purpose of this study is to determine whether or not the sympathetic nervous system provides a tonic inhibitory input to the colon in chloralose-anesthetized cats. Proximal and midcolonic motility were monitored using extraluminal force transducers. An intravenous bolus injection of 5 mg of phentolamine in 14 animals elicited a pronounced increase in proximal colon contractility. The minute motility index changed from 0 +/- 0 to 26 +/- 4 after phentolamine administration. Midcolonic motility also increased in response to phentolamine. Specific blockade of alpha 2-receptors, but not alpha 1-receptors, caused the same response seen with phentolamine. alpha-Adrenergic blockade increased colon contractility after spinal cord transection but not after ganglionic blockade. Blockade of alpha-adrenergic receptors was also performed before vagal and pelvic nerve stimulation and in both cases increased colonic motility. Vagal stimulation alone had no effect on colonic contractility, while pelvic nerve stimulation increased motility at the midcolon. alpha-Receptor blockade did not alter the ineffectiveness of vagal stimulation but did unmask excitatory effects of pelvic nerve stimulation on the proximal colon. All excitatory colonic responses were prevented by blocking muscarinic cholinergic receptors. These data indicate that tonic sympathetic nervous system activity exerts an inhibitory effect on colonic motility. The inhibitory effect is mediated through alpha 2-adrenergic receptors. Based on these findings, we suggest that alterations in sympathetic nervous system activity may be extremely important for the regulation of circular muscle contractions in the colon.

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