A Stimulus Independent Generator Function Focused Upon Merkel Cell and Neurite Currents of the Slowly Adapting Type I Cutaneous Afferent 586 views

The slowly adapting type I (SAI) cutaneous afferent innervates Merkel cells and their associated neurites, which constitute its architecture as a branching end organ. It is presently unknown how Merkel cells and neurites contribute, respectively, with receptor currents on different timescales, to the slow adaptation observed in elicited trains of action potentials. Due to the inherent difficulty of direct measurement, this effort in computational modeling is inspired by recent findings for Piezo2 mechanically activated channels in mice. The developed generator function includes components of a Merkel cell mechanism (slower decay of current) and a neurite mechanism (faster decay of current). Each of these functions takes as its input instantaneous stress in the skin, which each linearly convolves with its prior accumulation of decaying current over time. Summed together, recent time histories of stimulus magnitude and rate, as receptor current, are carried to the present. When the Merkel cell mechanism is removed in the context of simulating the entire end organ of the SAI afferent, its characteristic response of sustained spike firing over the hold of the stimulus is attenuated, as is observed for Piezo2 deficient animals. Furthermore, while prior models have directly converted the time derivatives of stimulus position into receptor current, this function uses biological mechanisms to make such conversions, and therefore is not fitted to or dependent on a particular stimulus.

MS (Master of Science)

English

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2015-07-30