Biology subjects

Abraham, I.

Publications and source records attributed to Abraham, I..

2 recordsLinked to original sources

bioRxiv2020

Live cell imaging of single neurotrophin receptor molecules on human neuron in Alzheimer's disease

The changes in the receptor dynamics such as the surface movement of the receptor molecules on the plasma membrane are essential to receptor function. However, whether the receptor dynamics are affected by disease conditions is unknown. Neurotrophin receptors such as TrkA and p75NTR play a critical role in neuronal survival and their functions are highly affected in Alzheimers disease (AD). Using live-cell single-molecule imaging of neurotrophin receptors we examined the surface trafficking of TrKA and p75NTR molecules on human induced pluripotent stem cells (hiPSCs) derived live neurons from presenilin 1 (PSEN1) mutant AD patients and healthy subjects. Here we report that surface trafficking of p75NTR molecules on neurites is faster than that of TrkA molecules in healthy controls. The surface dynamics of TrkA molecules were elevated in AD patients compared to healthy individuals. In contrast, the surface movement of p75NTR was significantly smaller in AD patients compared to healthy individuals. Interestingly, amyloid beta1-42 (A{beta}1-42) administration increased the surface trafficking of both TrkA and p75NTR in healthy hiPSCs neurons. These findings provides the first evidence that the surface diffusion of TrkA and p75NTR molecules are altered in patients suffering from AD. Our data also suggest that A{beta}1-42 may responsible for the alteration of the surface movements of TrkA but not for p75NTR. One Sentence SummaryThe surface movements of neurotrophin receptors such as TrkA and p75NTR are altered in neurons derived from patients suffering from familial Alzheimers disease.

neuroscience↗

bioRxiv2019

WHISKiT Physics: A three-dimensional mechanical model of the rat vibrissal array

Rodents tactually explore the environment using ~62 whiskers (vibrissae), regularly arranged in arrays on both sides of the face. The rat vibrissal system is one of the most commonly used models to study how the brain encodes and processes somatosensory information. To date, however, researchers have been unable to quantify the mechanosensory input at the base of each whisker, because the field lacks accurate models of three-dimensional whisker dynamics. To close this gap, we developed WHISKiT Physics, a simulation framework that incorporates realistic morphology of the full rat whisker array to predict time-varying mechanical signals for all whiskers. The dynamics of single whiskers were optimized based on experimental data, and then validated against free tip oscillations and the dynamic response to collision. The model is then extrapolated to include all whiskers in the array, taking into account each whiskers individual geometry. Simulations of first mode resonances across the array approximately match previous experimental results and fall well within the range expected from biological variability. Finally, we use WHISKiT Physics to simulate mechanical signals across the array during three distinct behavioral conditions: passive whisker stimulation, active whisking against two pegs, and active whisking in a natural environment. The results demonstrate that the simulation system can be used to predict input signals during a variety of behaviors, something that would be difficult or impossible in the biological animal. In all behavioral conditions, interactions between array morphology and individual whisker geometry shape the tactile input to the whisker system.

neuroscience↗