Abstract
Neural interfaces are designed to decode motor intent and evoke sensory precepts in amputees. In peripheral nerves, recording movement intent is challenging because motor axons are only a small fraction compared to sensory fibers and are heterogeneously mixed particularly at proximal levels. We previously reported that pain and myelinated axons regenerating through a Y-shaped nerve guide with sealed ends, can be modulated by luminar release of nerve growth factor (NGF) and neurotrophin-3 (NT-3), respectively. Here, we evaluate the differential potency of NGF, glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), pleiotrophin (PTN), and NT-3 in asymmetrically guiding the regeneration of sensory and motor neurons. We report that, in the absence of distal target organs, molecular guidance cues can mediate the growth of electrically conductive fascicles with normal microanatomy. Compared to Y-tube compartments with bovine serum albumin (BSA), GDNF and NGF increased the motor and sensory axon content, respectively. In addition, the sensory to motor ratio was significantly increased by PTN (12.7:1) when compared to a BDNF + GDNF choice. The differential content of motor and sensory axons modulated by selective guidance cues may provide a strategy to better define axon types in peripheral nerve interfaces.
Highlights
Several electrode configurations have been developed to interface with peripheral nerves, including extraneural cuffs, intrafascicular electrode arrays, and regenerative based electrodes[8,9]
We have shown that peripheral nerves can be directed to grow through an 18-electrode array placed in the lumen of a conduit[19,20]
Pain and temperature related sensory fibers are attracted by gradients of nerve growth factor (NGF), mechanoceptive neurons are influenced by brain-derived neurotrophic factor (BDNF), and neurotrophin- 3 (NT-3) is critical for reinnervation of proprioceptive neurons to muscle spindles[28,29,30,31,32]
Summary
Several electrode configurations have been developed to interface with peripheral nerves, including extraneural cuffs, intrafascicular electrode arrays, and regenerative based electrodes[8,9]. We have shown that peripheral nerves can be directed to grow through an 18-electrode array placed in the lumen of a conduit[19,20] This regenerative multi-electrode interface (REMI) records single units as early as 7 days from both motor and sensory sub-modality axons from animals in which the interfaced nerves are allowed to reinnervate their original target in the skin and muscle[21]. Given the critical role of neurotrophic factors (NTFs) from Schwann cells, muscle and skin targets, both during early development and post-injury in the adult peripheral nervous system (PNS)[22,23,24], we have proposed that such guidance cues can be used in regenerative neural interfaces to influence the selective interaction of motor and sensory subtype-axons with distinct electrodes. The sensory-to-motor (S/M) ratio of regenerated axons was significantly increased in the PTN loaded side of the Y-conduit compared to the BDNF + GDNF compartment
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