title: Spatial temperature gradients guide axonal outgrowth.
abstract: Formation of neural networks during development and regeneration after injury depends on accuracy of axonal pathfinding, which is primarily believed to be influenced by chemical cues. Recently, there is growing evidence that physical cues can play crucial role in axonal guidance. However, detailed mechanism involved in such guidance cues is lacking. By using weakly-focused near-infrared continuous wave (CW) laser microbeam in the path of an advancing axon, we discovered that the beam acts as a repulsive guidance cue. Here, we report that this highly-effective at-a-distance guidance is the result of a temperature field produced by the near-infrared laser light absorption. Since light absorption by extracellular medium increases when the laser wavelength was red shifted, the threshold laser power for reliable guidance was significantly lower in the near-infrared as compared to the visible spectrum. The spatial temperature gradient caused by the near-infrared laser beam at-a-distance was found to activate temperature-sensitive membrane receptors, resulting in an influx of calcium. The repulsive guidance effect was significantly reduced when extracellular calcium was depleted or in the presence of TRPV1-antagonist. Further, direct heating using micro-heater confirmed that the axonal guidance is caused by shallow temperature-gradient, eliminating the role of any non-photothermal effects.
authors.affiliation: Biophysics and Physiology Lab, Department of Physics, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Black
authors.affiliation: Department of Mechanical &Aerospace Engineering, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Vishwakarma
authors.affiliation: Biophysics and Physiology Lab, Department of Physics, USA.
authors.forename: Kamal
authors.initials: K
authors.lastname: Dhakal
authors.affiliation: Department of Bioengineering, The University of Texas at Arlington, TX 76019, USA.
authors.forename: Samik
authors.initials: S
authors.lastname: Bhattarai
authors.affiliation: Department of Physics, University of Memphis, TN 38152, USA.
authors.forename: Prabhakar
authors.initials: P
authors.lastname: Pradhan
authors.affiliation: Department of Mechanical &Aerospace Engineering, USA.
authors.forename: Ankur
authors.initials: A
authors.lastname: Jain
authors.affiliation: Department of Bioengineering, The University of Texas at Arlington, TX 76019, USA.|Department of Urology, UT Southwestern Medical Center, TX, USA.
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Kim
authors.affiliation: Biophysics and Physiology Lab, Department of Physics, USA.|Nanoscope Technologies, TX 76012, USA.
authors.forename: Samarendra
authors.initials: S
authors.lastname: Mohanty
mesh_terms: D000818:Animals; D000071437:Axon Guidance; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D051381:Rats; D013696:Temperature