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RESEARCH HIGHLIGHTS
Nature Reviews Gastroenterology & Hepatology 9, 244 (2012); published online 27 March 2012; doi:10.1038/nrgastro.2012.56

NEUROGASTROENTEROLOGY

New approach enables live recordings of nerve activity
in intestinal biopsy samples
Intestinal biopsy samples taken during
routine endoscopy provide enough viable
human enteric neurons to enable live
recordings of enteric neuron activity via
calcium (Ca2+) imaging. “By combining
precise microdissection and Ca2+ imaging,
we were able to record nerve activity in
human neurons wired in their original
environment,” says Pieter Vanden Berghe,
corresponding author of this recent study.
Although other researchers have studied
the activity of human enteric neurons,
they have been restricted to using surgical
tissue samples, which are from patients
with severe disease and are of limited
availability. Vanden Berghe and colleagues
Carla Cirillo and Jan Tack developed
their method to circumvent limited tissue
availability and the presence of diseaselinked confounding factors. “Performing
biopsies can be considered low risk and
rather noninvasive; therefore, this method
makes it possible to investigate human
nerve activity from a wide variety of

Human intestinal neurons in an intestinal biopsy sample,
labeled with three different neuronal markers: NF200 (red),
HuC/D (green) and β-tubulin (blue). Scale bar = 20 µm. Image
courtesy of P Vanden Berghe.
.

patients and even volunteers,” explains
Vanden Berghe.
Analysis of 72 duodenal biopsy
samples (from 48 patients referred for
evaluation of presumed functional
gastrointestinal disorders) identified an
average of 7.7 ± 6.0 ganglia, 35.1 ± 25.3
neurons and 2.1 ± 1.8 isolated neurons
per biopsy sample. Neurons could be
activated by exogenous application of a

NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY 	
© 2012 Macmillan Publishers Limited. All rights reserved

nicotinic cholinergic receptor agonist or
serotonin, or by electrical stimulation of
interganglionic fiber tracts. Tetrodotoxin
and zero-Ca2+ solution were both able to
suppress these responses in part or in full.
The researchers are now using
their technique to see whether enteric
neuron function is affected in specific
gastrointestinal disorders. They also
suggest that it could be used to study
the physiological properties of enteric
neurons in the setting of gastrointestinal
and neurological diseases in general. “This
method also offers the opportunity to
perform drug testing on human neurons
and may be a first step in the development
of testing personalized drug treatment,”
concludes Vanden Berghe.
Natalie J. Wood
Original article Cirillo, C. et al. Nerve activity recordings
in routine human intestinal biopsies. Gut doi:10.1136/
gutjnl-2011-301777

VOLUME 9  |  MAY 2012

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Nrgastro.2012.56

  • 1. RESEARCH HIGHLIGHTS Nature Reviews Gastroenterology & Hepatology 9, 244 (2012); published online 27 March 2012; doi:10.1038/nrgastro.2012.56 NEUROGASTROENTEROLOGY New approach enables live recordings of nerve activity in intestinal biopsy samples Intestinal biopsy samples taken during routine endoscopy provide enough viable human enteric neurons to enable live recordings of enteric neuron activity via calcium (Ca2+) imaging. “By combining precise microdissection and Ca2+ imaging, we were able to record nerve activity in human neurons wired in their original environment,” says Pieter Vanden Berghe, corresponding author of this recent study. Although other researchers have studied the activity of human enteric neurons, they have been restricted to using surgical tissue samples, which are from patients with severe disease and are of limited availability. Vanden Berghe and colleagues Carla Cirillo and Jan Tack developed their method to circumvent limited tissue availability and the presence of diseaselinked confounding factors. “Performing biopsies can be considered low risk and rather noninvasive; therefore, this method makes it possible to investigate human nerve activity from a wide variety of Human intestinal neurons in an intestinal biopsy sample, labeled with three different neuronal markers: NF200 (red), HuC/D (green) and β-tubulin (blue). Scale bar = 20 µm. Image courtesy of P Vanden Berghe. . patients and even volunteers,” explains Vanden Berghe. Analysis of 72 duodenal biopsy samples (from 48 patients referred for evaluation of presumed functional gastrointestinal disorders) identified an average of 7.7 ± 6.0 ganglia, 35.1 ± 25.3 neurons and 2.1 ± 1.8 isolated neurons per biopsy sample. Neurons could be activated by exogenous application of a NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY © 2012 Macmillan Publishers Limited. All rights reserved nicotinic cholinergic receptor agonist or serotonin, or by electrical stimulation of interganglionic fiber tracts. Tetrodotoxin and zero-Ca2+ solution were both able to suppress these responses in part or in full. The researchers are now using their technique to see whether enteric neuron function is affected in specific gastrointestinal disorders. They also suggest that it could be used to study the physiological properties of enteric neurons in the setting of gastrointestinal and neurological diseases in general. “This method also offers the opportunity to perform drug testing on human neurons and may be a first step in the development of testing personalized drug treatment,” concludes Vanden Berghe. Natalie J. Wood Original article Cirillo, C. et al. Nerve activity recordings in routine human intestinal biopsies. Gut doi:10.1136/ gutjnl-2011-301777 VOLUME 9  |  MAY 2012