Computation predicts rapidly adapting mechanotransduction currents cannot account for tactile encoding in Merkel...

Area of Science:

• Neuroscience
• Biophysics
• Computational Biology

Background:

• Merkel cells and their associated neurites are crucial for touch sensation (SAI afferents).
• The mechanism by which rapidly inactivating currents produce sustained firing in SAI afferents is not fully understood.
• Piezo2 channels are essential in both Merkel cells and sensory neurons for SAI responses.

Purpose of the Study:

• To computationally model mechanotransduction currents in Merkel cells and neurites.
• To explain sustained action potential firing in SAI afferents.
• To replicate firing patterns in wildtype and Atoh1 knockout mice.

Main Methods:

• Developed a computational model synthesizing mechanotransduction currents from Merkel cells and neurites.
• Incorporated skin mechanics and neural dynamics into the model.
• Modeled Merkel cell and neurite-specific current properties, including voltage-activated conductances.

Main Results:

• The model successfully mimicked distinct firing patterns of wildtype and Atoh1 knockout animals.
• A longer time constant than observed for Merkel cell depolarization was required for sustained firing.
• Introducing an ultra-slowly inactivating current (1.7s time constant) in the sensory neuron replicated slow adaptation.

Conclusions:

• An ultra-slowly inactivating current within the sensory neuron, not solely skin mechanics, likely drives slow adaptation in SAI afferents.
• This model reconciles the physiology and anatomy of Merkel cell function in touch sensation.
• The findings provide insights into the distinct firing properties of touch receptors.