Strategies for interfacing with the trigeminal nerves in rodents for bioelectric medicine

Bioelectric medicine seeks to modulate neural activity via targeted electrical stimulation to treat disease. Recent clinical evidence supports trigeminal nerve stimulation as a bioelectric treatment for several neurological disorders; however, the mechanisms of trigeminal nerve stimulation and potential side effects remain largely unknown. The goal of this study is to optimize the methodology and reproducibility of neural interface implantation for mechanistic studies in rodents. This article describes a single incision surgical approach to the infraorbital nerve of rats and mice and the supraorbital nerve in rats for trigeminal nerve stimulation studies. This article also presents the use of cortical evoked potentials and electromyography as methods for demonstrating effective engagement between the implanted electrode and target nerve. A number of surgical approaches to the infraorbital nerve in rats exist, many of which are technically difficult. A simple, standardized approach to infraorbital nerve in rats and mice, as well as the supraorbital nerve of rats is integral to reproducibility of future trigeminal nerve stimulation studies. The infraorbital nerve of rats and mice can be easily accessed from a single dorsal incision on the bridge of the nose that avoids major anatomical structures such as the facial nerve. The supraorbital nerve is also accessible in rats from a single dorsal incision, but not mice due to size. Successful interfacing and engagement of the infra- and supraorbital nerves using the described methodology is demonstrated by recording of evoked cortical potentials and electromyography.