Abstract

Mechanical forces are increasingly recognized as major regulators of several physiological processes at both the molecular and cellular level; therefore, a deep understanding of the sensing of these forces and their conversion into electrical signals are essential for studying the mechanosensitive properties of soft biological tissues. To contribute to this field, we present a dual-purpose device able to mechanically stimulate retinal tissue and to record the spiking activity of retinal ganglion cells (RGCs). This new instrument relies on combining ferrule-top micro-indentation, which provides local measurements of viscoelasticity, with high-density multi-electrode array (HD-MEAs) to simultaneously record the spontaneous activity of the retina. In this paper, we introduce this instrument, describe its technical characteristics, and present a proof-of-concept experiment that shows how RGC spiking activity of explanted mice retinas respond to mechanical micro-stimulations of their photoreceptor layer. The data suggest that, under specific conditions of indentation, the retina perceive the mechanical stimulation as modulation of the visual input, besides the longer time-scale of activation, and the increase in spiking activity is not only localized under the indentation probe, but it propagates across the retinal tissue.

Highlights

  • Eukaryotic cells are constantly subjected to biomechanical interactions with the extracellular environment

  • Under specific indentation conditions, mechanical stimulation can induce a response in a subset of retinal ganglion cells (RGCs), suggesting that the retina integrates the effects of biomechanical forces when encoding visual inputs

  • The primary purpose of this study was to design a new experimental setup able to combine a HD-MEAs with ferrule top indentation to provide insights about electromechanical coupling in retina tissue

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Summary

Introduction

Eukaryotic cells are constantly subjected to biomechanical interactions with the extracellular environment. Biomechanical forces exerted on cells in the brain have important, yet partially understood effects on the physiological development and functional behavior of brain. Neurons and glial cells are embodied in brain circuits, and intrinsically experience physical cues due to their surrounding physical world, which include, among others, electrochemical gradients and mechanical stresses (Tyler, 2012; Franze, 2018). Mechanotransduction can influence several cellular processes in the brain, including differentiation, survival, proliferation, and migration, contributing to its physiological or pathophysiological development (Ingber, 2003). The role of cellular mechanotransduction has been associated with cellular and sub-cellular injuries that may lead to the diffusion of pathological damage in traumatic brain injury (Hemphill et al, 2015). Biomechanical forces are involved in cerebral cortical folding as well as in folding abnormalities in neurodevelopmental brain disorders

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