Selective stimulation of the ferret abdominal vagus nerve with multi-contact nerve cuff electrodes

Jonathan A Shulgach,Stephanie Fulton,John Ogren,Michael Sciullo,Bill J Yates,Derek M Miller,Ameya C Nanivadekar,Lee E Fisher,Liane Wong,Charles C Horn,Dylan W Beam,Bryan L Mclaughlin

doi:10.1038/s41598-021-91900-1

Abstract

Dysfunction and diseases of the gastrointestinal (GI) tract are a major driver of medical care. The vagus nerve innervates and controls multiple organs of the GI tract and vagus nerve stimulation (VNS) could provide a means for affecting GI function and treating disease. However, the vagus nerve also innervates many other organs throughout the body, and off-target effects of VNS could cause major side effects such as changes in blood pressure. In this study, we aimed to achieve selective stimulation of populations of vagal afferents using a multi-contact cuff electrode wrapped around the abdominal trunks of the vagus nerve. Four-contact nerve cuff electrodes were implanted around the dorsal (N = 3) or ventral (N = 3) abdominal vagus nerve in six ferrets, and the response to stimulation was measured via a 32-channel microelectrode array (MEA) inserted into the left or right nodose ganglion. Selectivity was characterized by the ability to evoke responses in MEA channels through one bipolar pair of cuff contacts but not through the other bipolar pair. We demonstrated that it was possible to selectively activate subpopulations of vagal neurons using abdominal VNS. Additionally, we quantified the conduction velocity of evoked responses to determine what types of nerve fibers (i.e., Aδ vs. C) responded to stimulation. We also quantified the spatial organization of evoked responses in the nodose MEA to determine if there is somatotopic organization of the neurons in that ganglion. Finally, we demonstrated in a separate set of three ferrets that stimulation of the abdominal vagus via a four-contact cuff could selectively alter gastric myoelectric activity, suggesting that abdominal VNS can potentially be used to control GI function.

Highlights

Dysfunction and diseases of the gastrointestinal (GI) tract are a major driver of medical care
The primary goal of this study was to determine whether subpopulations of axons in the abdominal vagus nerve could be selectively activated as a means to control GI function while avoiding off-target side effects
A cuff electrode with two bipolar pairs of contacts (Fig. 1) was wrapped around the dorsal (N = 3) or ventral (N = 3) abdominal vagus nerve, and the response to stimulation was measured by recording evoked compound action potential (CAP) through a 32-channel microelectrode array (MEA) implanted into the nodose ganglion[24]

Summary

Introduction

Dysfunction and diseases of the gastrointestinal (GI) tract are a major driver of medical care. We aimed to achieve selective stimulation of populations of vagal afferents using a multi-contact cuff electrode wrapped around the abdominal trunks of the vagus nerve. Four-contact nerve cuff electrodes were implanted around the dorsal (N = 3) or ventral (N = 3) abdominal vagus nerve in six ferrets, and the response to stimulation was measured via a 32-channel microelectrode array (MEA) inserted into the left or right nodose ganglion. Techniques that quantify selectivity by measuring effects on end-organ function or by recording evoked responses in nerve branches are highly challenging because the vagus nerve branches are small, variable, and often inaccessible; they innervate organs throughout the abdomen[19]. Action potentials can be recorded from these cell bodies using microelectrode arrays (MEA)[22]

Objectives

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Results

Conclusion