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Amplification and temporal filtering during gradient sensing by nerve growth cones probed with a microfluidic assay
Mathieu Morel1, Vasyl Shynkar, Jean-Christophe Galas
1Laboratoire 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.
Biophysical Journal
|October 23, 2012
Summary
Nerve growth cones amplify and filter chemical signals through GABA(A) receptor dynamics. This study reveals how these crucial neuronal structures process external cues for directed growth.
Area of Science:
- Neuroscience
- Cell Biology
- Biophysics
Background:
- Nerve growth cones (GCs) are essential for neuronal development, translating external chemical signals into directed growth.
- The mechanisms by which GCs amplify and filter complex chemical gradients remain largely unknown.
- Understanding GC signal processing is critical for deciphering neural circuit formation.
Purpose of the Study:
- To investigate the signal-processing capabilities of single nerve growth cones during directional sensing of gamma-Aminobutyric acid (GABA).
- To elucidate the molecular mechanisms underlying GC amplification and filtering of external cues.
- To correlate single-molecule receptor dynamics with systems-level GC responses.
Main Methods:
- Utilized a shear-free microfluidic assay for precise control of external GABA gradients.
- Measured single-molecule polarization of GABA(A) chemoreceptors at the GC membrane.
- Employed computational modeling to link molecular dynamics to GC behavior.
Main Results:
- Nerve growth cones exhibit signal amplification within specific GABA concentration ranges.
- GCs function as low-pass temporal filters, with a consistent cutoff frequency.
- Molecular-level analysis revealed that saturable receptor occupancy and lateral receptor dynamics drive these processing properties.
Conclusions:
- Nerve growth cones possess sophisticated signal-processing abilities, acting as amplifiers and filters.
- GABA(A) receptor dynamics at the molecular level are key to GC signal transduction.
- These findings provide fundamental insights into axonal guidance and neuronal development.
