Neurogenic and myogenic patterns of electrical activity in isolated intact mouse colon

Hibberd, Timothy J.; Costa, Marcello; Travis, Lee Edward; Brookes, Simon Jonathan; Wattchow, David; Feng, Jing; Hu, Hongzhen; Spencer, Nick J.

doi:10.1111/nmo.13089

Cited by 42 publications

(35 citation statements)

References 61 publications

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“…In this study, stretch in the proximal colon induced hyperpolarization of the muscle cells which was inhibited in the presence of TTX and L‐NNA. In addition, tissue dissection and shortening of colon tissue as reported by Hibberd et al can cause excessive NO release and might also underlie the differences in frequency. Nevertheless, both experimental conditions (colon rings and whole colon) revealed NO‐mediated regulation of LDC frequency.…”

Section: Discussionmentioning

confidence: 93%

Cell‐specific effects of nitric oxide on the efficiency and frequency of long distance contractions in murine colon

Beck

Voussen

Reigl

et al. 2019

Neurogastroenterology Motil

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Background Nitric oxide (NO) mediates inhibitory neurotransmission and is a critical component of neuronal programs that generate propulsive contractions. NO acts via its receptor NO‐sensitive guanylyl cyclase (NO‐GC) which is expressed in smooth muscle cells (SMC) and interstitial cells of Cajal (ICC). Organ bath studies with colonic rings from NO‐GC knockout mice (GCKO) have indicated NO‐GC to modulate spontaneous contractions. The cell‐specific effects of NO‐GC on the dominant pan‐colonic propulsive contraction, the long distance contractions (LDCs), of whole colon preparations have not yet been described. Methods Contractions of whole colon preparations from wild type (WT), global, and cell‐specific GCKO were recorded. After transformation into spatiotemporal maps, motility patterns were analyzed. Simultaneous perfusion of the colon enabled the correlation of outflow with LDCs to analyze contraction efficiency. Key Results Deletion of NO‐GC in both ICC and SMC (ie, in GCKO and SMC/ICC‐GCKO) caused loss of typical LDC activity and instead generated high‐frequency LDC‐like contractions with inefficient propulsive activity. Frequency was also increased in WT, SMC‐GCKO, and ICC‐GCKO colon in the presence of L‐NAME to block neuronal NO synthase. LDC efficiency was dependent on NO‐GC in SMC as it was reduced in GCKO, SMC‐GCKO, and ICC/SMC‐GCKO colon; LDC efficiency was decreased in all genotypes in the presence of L‐NAME. Conclusions and Inferences NO/cGMP signaling is critical for normal peristaltic movements; as NO‐GC in both SMC and ICC is essential, both cell types appear to work in synchrony. The efficiency of contractions to expel fluid is particularly influenced by NO‐GC in SMC.

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Section: Discussionmentioning

confidence: 93%

Cell‐specific effects of nitric oxide on the efficiency and frequency of long distance contractions in murine colon

Beck

Voussen

Reigl

et al. 2019

Neurogastroenterology Motil

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“…In rodents, colonic motor patterns involve three types of contractions: ripples, slow phasic contractions (SPC), and sporadic neurogenic contractions probably related to neurogenic Colonic Motor Complexes . These three patterns coordinate colonic mechanisms such as segmentation and peristalsis.…”

Section: Discussionmentioning

confidence: 99%

“…Complexes. [22][23][24] These three patterns coordinate colonic mechanisms such as segmentation and peristalsis. All of them can be recorded in vitro, even in small strips, with a force transducer that measures contractility from the circular muscle.…”

Section: Discussionmentioning

confidence: 99%

The asymmetric innervation of the circular and longitudinal muscle of the mouse colon differently modulates myogenic slow phasic contractions

Traserra

Villarte

Traini

et al. 2019

Neurogastroenterology Motil

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Background Neuromuscular transmission has been extensively studied in the circular layer of the mouse colon where a co‐transmission of purines acting on P2Y1 receptors and NO has been previously described. However, the corresponding mechanisms in the longitudinal layer are less known. Methods Electrophysiological and myography techniques were used to evaluate spontaneous phasic contractions (SPC) and neural‐mediated responses in the proximal, mid, and distal colon devoid of CD1 mice. Immunohistochemistry against c‐kit and PDGFRα was performed in each colonic segment. Key Results SPC were recorded in both muscle layers at a similar frequency being about four contractions per minute (c.p.m.) in the proximal and distal colon compared to the mid colon (2 c.p.m.). In non‐adrenergic, non‐cholinergic conditions, L‐NNA (1 mmol/L) increased contractility in the circular but not in the longitudinal layer. In the longitudinal muscle, both electrophysiological and mechanical neural‐mediated inhibitory responses were L‐NNA and ODQ (10 µmol/L) sensitive. NaNP (1 µmol/L) caused cessation of SPC and the response was blocked by ODQ. Neither ADPßS (10 µmol/L) nor CYPPA (10 µmol/L), which both targeted the purinergic pathway, altered longitudinal contractions. PDGFRα + cells were located in both muscle layers and were more numerous compared with cKit + cells, which both formed a heterologous cellular network. A decreasing gradient of the PDGFRα labeling was observed along the colon. Conclusion An inhibitory neural tone was absent in the longitudinal layer and neuronal inhibitory responses were mainly nitrergic. Despite the presence of PDGFRα + cells, purinergic responses were absent. Post‐junctional pathways located in different cell types might be responsible for neurotransmitter transduction.

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“…The ENS consists of millions of neurons that are contained within interconnected micro-ganglia that form two distinct plexuses, known as the myenteric and submucosal plexuses (Furness, 2006;Wood, 2012). Much has been learnt about the different types of neurons within the ENS (Costa et al, 1996;Furness, 2006), particularly in guinea pig ileum (Costa and Brookes, 1994), including their neuronal projections and synaptic inputs and outputs (Bornstein et al, 1994;Furness et al, 1998;Furness, 2006;Mazzuoli and Schemann, 2012;Wood, 2012;Mazzuoli-Weber and Schemann, 2015). In mammals, the neurons responsible for coordinating motor behavior along the intestine are located in the myenteric plexus and include inhibitory and excitatory motor neurons, ascending and descending interneurons, and a unique population of intrinsic sensory neurons only found in the GI tract (Furness et al, 1998;Mazzuoli andSchemann, 2009, 2012;Mazzuoli-Weber and Schemann, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Much has been learnt about the different types of neurons within the ENS (Costa et al, 1996;Furness, 2006), particularly in guinea pig ileum (Costa and Brookes, 1994), including their neuronal projections and synaptic inputs and outputs (Bornstein et al, 1994;Furness et al, 1998;Furness, 2006;Mazzuoli and Schemann, 2012;Wood, 2012;Mazzuoli-Weber and Schemann, 2015). In mammals, the neurons responsible for coordinating motor behavior along the intestine are located in the myenteric plexus and include inhibitory and excitatory motor neurons, ascending and descending interneurons, and a unique population of intrinsic sensory neurons only found in the GI tract (Furness et al, 1998;Mazzuoli andSchemann, 2009, 2012;Mazzuoli-Weber and Schemann, 2015). Despite a detailed knowledge of these neurons, a major unresolved mystery is how such a large population of neurons behave during the neurogenic motor behaviors that propel content along the bowel (Wood, 2008(Wood, , 2016Hu and Spencer, 2018).…”

Section: Introductionmentioning

confidence: 99%

Identification of a Rhythmic Firing Pattern in the Enteric Nervous System That Generates Rhythmic Electrical Activity in Smooth Muscle

et al. 2018

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The enteric nervous system (ENS) contains millions of neurons essential for organization of motor behavior of the intestine. It is well established that the large intestine requires ENS activity to drive propulsive motor behaviors. However, the firing pattern of the ENS underlying propagating neurogenic contractions of the large intestine remains unknown. To identify this, we used high-resolution neuronal imaging with electrophysiology from neighboring smooth muscle. Myoelectric activity underlying propagating neurogenic contractions along murine large intestine [also referred to as colonic migrating motor complexes, (CMMCs)] consisted of prolonged bursts of rhythmic depolarizations at a frequency of ∼2 Hz. Temporal coordination of this activity in the smooth muscle over large spatial fields (∼7 mm, longitudinally) was dependent on the ENS. During quiescent periods between neurogenic contractions, recordings from large populations of enteric neurons, in mice of either sex, revealed ongoing activity. The onset of neurogenic contractions was characterized by the emergence of temporally synchronized activity across large populations of excitatory and inhibitory neurons. This neuronal firing pattern was rhythmic and temporally synchronized across large numbers of ganglia at ∼2 Hz. ENS activation preceded smooth muscle depolarization, indicating rhythmic depolarizations in smooth muscle were controlled by firing of enteric neurons. The cyclical emergence of temporally coordinated firing of large populations of enteric neurons represents a unique neural motor pattern outside the CNS. This is the first direct observation of rhythmic firing in the ENS underlying rhythmic electrical depolarizations in smooth muscle. The pattern of neuronal activity we identified underlies the generation of CMMCs. How the enteric nervous system (ENS) generates neurogenic contractions of smooth muscle in the gastrointestinal (GI) tract has been a long-standing mystery in vertebrates. It is well known that myogenic pacemaker cells exist in the GI tract [called interstitial cells of Cajal (ICCs)] that generate rhythmic myogenic contractions. However, the mechanisms underlying the generation of rhythmic neurogenic contractions of smooth muscle in the GI tract remains unknown. We developed a high-resolution neuronal imaging method with electrophysiology to address this issue. This technique revealed a novel pattern of rhythmic coordinated neuronal firing in the ENS that has never been identified. Rhythmic neuronal firing in the ENS was found to generate rhythmic neurogenic depolarizations in smooth muscle that underlie contraction of the GI tract.

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Neurogenic and myogenic patterns of electrical activity in isolated intact mouse colon

Cited by 42 publications

References 61 publications

Cell‐specific effects of nitric oxide on the efficiency and frequency of long distance contractions in murine colon

Cell‐specific effects of nitric oxide on the efficiency and frequency of long distance contractions in murine colon

The asymmetric innervation of the circular and longitudinal muscle of the mouse colon differently modulates myogenic slow phasic contractions

Identification of a Rhythmic Firing Pattern in the Enteric Nervous System That Generates Rhythmic Electrical Activity in Smooth Muscle

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