Gastric Distension‐induced Nodose Ganglionic Cell Responses Using a High‐throughput Multi‐electrode Array in the Ferret

Abstract

The nodose ganglion (NG) contains cell bodies of gastrointestinal afferents, which play critical roles in metabolic and feeding disorders and gastrointestinal and inflammatory diseases. To further understand the population coding of nodose ganglionic signals, we used a 32‐chan multi‐electrode array (MEA; 4×8, 400 μm pitch; Blackrock Microsystems) to record single‐unit responses with 3 main objectives: (1) determine the stability of multiple single‐unit responses during several hours of in vivo electrophysiological recording; (2) measure the activation patterns of these neurons to prototypical stimulation, such as gastric distension; and (3) investigate the phenotypes of nodose neurons using mechanical probing and vagus nerve electrical stimulation to determine conduction velocities. Acute experiments were performed in anesthetized ferrets using inhalational isoflurane (~2.5%) anesthesia. MEAs were inserted in the nodose ganglion using a pneumatic inserter, and a balloon‐catheter was advanced into the stomach through a small incision on the lateral edge of the gastric fundus. Two volumes of saline, 10 and 20 ml, were infused into the balloon to provide distension. Nerve cuff electrodes were placed on the abdominal vagus trunk to determine conduction velocity. Ganglionic single‐unit activity was successfully recorded from the NG for up to 5.3 h. In our preliminary analysis using spike sorting on each channel (MKsort, https://github.com/ripple‐neuro/mksort; Matlab), we were able to identify a total of 233 units in 6 animals (16 to 55 units per animal). Gastric balloon distension produced >20% increase in neuronal activity in an average of 48% of units to 10 ml inflation and 56% of units to 20 ml inflation. These results demonstrate the feasibility to record multiple single‐unit responses from the ferret NG to provide insight into gastric‐related population coding. Future effort could focus on delineating the physiological roles of these gastric neurons for the design of neuromodulation devices, which could be used to treat diseases involving vagal sensory input such as obesity and the chronic nausea associated with gastroparesis.Support or Funding InformationThis research was supported by funding from the NIH SPARC Common Fund Program (award #U18TR002205).