Amplification and temporal filtering during gradient sensing by nerve growth cones probed with a microfluidic assay.
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.
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.
Mathieu
M
Morel
Vasyl
V
Shynkar
Jean-Christophe
JC
Galas
Isabelle
I
Dupin
Cedric
C
Bouzigues
Vincent
V
Studer
Maxime
M
Dahan
D000818:Animals; D020439:Growth Cones / Q000378:metabolism / Q000502:physiology*; D046210:Microfluidic Analytical Techniques; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism; D014981:Xenopus; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid