Amplification and Temporal Filtering during Gradient Sensing by Nerve Growth Cones Probed with a Microfluidic Assay
Biophysical Journal. 2012-10-01; 103(8): 1648-1656
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1. Biophys J. 2012 Oct 17;103(8):1648-56. doi: 10.1016/j.bpj.2012.08.040. Epub 2012
Amplification and temporal filtering during gradient sensing by nerve growth
cones probed with a microfluidic assay.
Morel M(1), Shynkar V, Galas JC, Dupin I, Bouzigues C, Studer V, Dahan M.
(1)Laboratoire Kastler Brossel, Centre National de la Recherche Scientifique,
Département de Physique and Institut de Biologie de l’Ecole normale supérieure,
Université Pierre et Marie Curie, Paris, France.
Nerve growth cones (GCs) are chemical sensors that convert graded extracellular
cues into oriented axonal motion. To ensure a sensitive and robust response to
directional signals in complex and dynamic chemical landscapes, GCs are
presumably able to amplify and filter external information. How these processing
tasks are performed remains however poorly known. Here, we probe the
signal-processing capabilities of single GCs during γ-Aminobutyric acid (GABA)
directional sensing with a shear-free microfluidic assay that enables systematic
measurements of the GC output response to variable input gradients. By measuring
at the single molecule level the polarization of GABA(A) chemoreceptors at the GC
membrane, as a function of the external GABA gradient, we find that GCs act as
i), signal amplifiers over a narrow range of concentrations, and ii), low-pass
temporal filters with a cutoff frequency independent of stimuli conditions. With
computational modeling, we determine that these systems-level properties arise at
a molecular level from the saturable occupancy response and the lateral dynamics
of GABA(A) receptors.
Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights
PMID: 23083707 [Indexed for MEDLINE]