Recording of Electrically Evoked Neural Activity and Bladder Pressure Responses in Awake Rats Chronically Implanted With a Pelvic Nerve Array

Abstract

Bioelectronic medical devices are well established and widely used in the treatment of urological dysfunction. Approved targets include the sacral S3 spinal root and posterior tibial nerve, but an alternate target is the group of pelvic splanchnic nerves, as these contain sacral visceral sensory and autonomic motor pathways that coordinate storage and voiding functions of the bladder. Here, we developed a device suitable for long-term use in an awake rat model to study electrical neuromodulation of the pelvic nerve (homolog of the human pelvic splanchnic nerves). In male Sprague-Dawley rats, custom planar four-electrode arrays were implanted over the distal end of the pelvic nerve, close to the major pelvic ganglion. Electrically evoked compound action potentials (ECAPs) were reliably detected under anesthesia and in chronically implanted, awake rats up to 8 weeks post-surgery. ECAP waveforms showed three peaks, with latencies that suggested electrical stimulation activated several subpopulations of myelinated A-fiber and unmyelinated C-fiber axons. Chronic implantation of the array did not impact on voiding evoked in awake rats by continuous cystometry, where void parameters were comparable to those published in naïve rats. Electrical stimulation with chronically implanted arrays also induced two classes of bladder pressure responses detected by continuous flow cystometry in awake rats: voiding contractions and non-voiding contractions. No evidence of tissue pathology produced by chronically implanted arrays was detected by immunohistochemical visualization of markers for neuronal injury or noxious spinal cord activation. These results demonstrate a rat pelvic nerve electrode array that can be used for preclinical development of closed loop neuromodulation devices targeting the pelvic nerve as a therapy for neuro-urological dysfunction.

Selective recording of physiologically evoked neural activity in a mixed autonomic nerve using a minimally invasive array

“…Stimulating the pelvic nerve with E1 and E2 [closest to the spine, Fig. 1(b) ] and recording from E3 and E4 (closest to the bladder, S12R34 in Table I ) evoked up to three distinct waveforms, categorized by latency, similar to that reported previously ( Payne et al , 2020 ). A representative example in Fig.…”

“…Recording of electrically evoked compound action potentials (ECAPs) is a long-standing method of recording electrically evoked neural activity in humans as a way of verifying stimulation is appropriately activating neural pathways ( van Dijk et al , 2007 ). Our own efforts show stable long-term recording of electrically evoked activity in the vagus nerve ( Payne et al , 2018 , 2019 , 2022 ) and pelvic nerve ( Payne et al , 2020 ; Eiber et al , 2021 ) of awake, freely moving animals for up to three months. In this study, up to three waveforms were recorded similar to that reported previously ( Payne et al , 2020 ).…”

“…Previously, we have developed a minimally invasive, extra-epineural neural interface and have recently reported that it can record electrically evoked neural activity ( Table I ) from two visceral nerves—the vagus ( Payne et al , 2018 , 2019 , 2022 ) and pelvic nerve ( Payne et al , 2020 ). Furthermore, we have shown our four-channel electrode “Longitudinal Interface Nerve Electrode” (LINE) device can be safely implanted onto a fragile visceral nerve for periods in excess of 8 weeks ( Payne et al , 2020 ). This array, therefore, provides another alternative for interfacing with small peripheral visceral nerves.…”

“…To address this limitation, this study investigated if a novel signal processing method (see details below) that runs cross-correlation analyses between two pairs of recordings ( Fallon, 2019 ) can extract physiologically evoked neural activity from signals recorded from a mixed autonomic nerve. To do this, we implanted our LINE devices on the pelvic nerve in adult male rats and physiologically evoked neural activity by continuous flow cystometry as reported previously ( Payne et al , 2020 ). The pelvic nerve of rats is well characterized as it is the primary visceral nerve used by lumbosacral afferents (sensory) and parasympathetic autonomic preganglionic efferents (visceral motor) to project to the bladder, distal colon, and reproductive organs ( Nadelhaft and Booth, 1984 ; Keast, 2006 ) [ Fig.…”

Brains in space: the importance of understanding the impact of long-duration spaceflight on spatial cognition and its neural circuitry

“…Operational performance can be assessed by simulating spaceflight-related tasks such as using robotic arms to capture a transiting spacecraft or to control a spacecraft to maneuver it and dock it to another vehicle (Ivkovic et al 2019 ; Johannes et al 2017 ). Successful completion of the maneuvers relates to various cognitive domains, including but not limited to situational awareness, planning, decision-making, object orientation, mental rotation, visual processing, fine motor control, and visual motor integration (Wong et al 2020 ). It can be hypothesized that complex tasks assessing the encoding, processing, storage, and retrieval of visuospatial information could be particularly vulnerable during spaceflight.…”