SPARC: Acute Glucose Regulation Recordings from the Rat Vagus Nerve Using Carbon Fiber Microelectrode Arrays
Authors: Jiman Ahmad A. , Ratze David C. , Welle Elissa J. , Patel Paras R. , Bottorff Elizabeth C. , Richie Julianna M. , Seymour John P. , Chestek Cynthia A. , Bruns Tim M. 
Published: April 2020

Glucose regulation is a vital continuous process for maintaining a healthy biological state. This requires complicated coordination between the endocrine and nervous systems. An important pathway in the peripheral nervous system for glucose regulation is the vagus nerve, as it innervates the liver and pancreas, which are the main organs for glucose regulation. However, limited information is available on the neural activity for glucose regulation that propagates through the vagus nerve. An electrode that has shown promising neural recording abilities with minimal tissue damage in the brain is the carbon fiber microelectrode array (CFMA). The objective of this study was to identify glucose regulation neural signals in the vagus nerve using CFMAs.

In this study, we performed non‐survival experiments on anesthetized, fasted Sprague‐Dawley rats. Through a midline ventral cervical incision, the left vagus nerve was isolated and placed on a custom 3D‐printed nerve‐holder. A CFMA (10–16 fibers; 200–250 μm in length; 132 μm pitch; 2‐row layout) was inserted in the vagus nerve and connected to a neural interface processor that recorded at a sampling rate of 30 kHz. A bolus of glucose (1 g) or insulin (20 U) was administered intraperitoneally to modulate blood glucose levels, or saline (1 mL) for control. Measurements of blood glucose concentrations from the tail were obtained every 5 minutes using a glucometer. Neural data was analyzed using Plexon Offline Sorter and MATLAB.

Glucose administration elevated blood glucose levels up to 114% above baseline. Observed neural units with firing rates up to 5 spikes/sec and peak‐to‐peak amplitudes of 31–43 μV decreased their firing rates after administration of glucose. These units may represent afferent signaling that were driven from fasting the animal, and the firing rates of these units decreased after glucose injection. Insulin administration decreased blood glucose levels by 34% from baseline. Approximately 2–5 minutes after insulin administration, units with amplitudes of 78–96 μV peak‐to‐peak were firing at rates up to 21 spikes/sec. These units may represent an increase in afferent activity to request glucose intake. In control experiments, observed units with amplitudes of 44–62 μV peak‐to‐peak maintained their firing rates of 5–9 spikes/s before and after administration of saline. These units may represent continuous afferent signaling to increase food intake or signaling that is not related to glucose regulation.

Overall, our results demonstrate that CFMA is a viable electrode for recording neural unit activity related to glucose regulation in the vagus nerve. Furthermore, this work suggests that the CFMA can be used to monitor neural unit activity in peripheral nerves to help better understand the neural regulation pathways in various physiological and pathophysiological conditions.

Support or Funding Information

This research was supported by the National Institute of Health SPARC Program (Award OT2OD024907) and the National Science Foundation (Award 1707316).