New imaging method shows details of brainstem activity

06 May 2025

Japan team develops two-prism implant to view brain's inaccessible NTS region.

A project at Japan's National Institute for Physiological Sciences has developed a new imaging component for viewing a region of the brain previously tricky to observe.

Christened double-prism-based brainstem imaging under cerebellar architecture and neural circuits (D-PSCAN), the details of the technique were published in Cell Reports Methods.

The goal in particular was to improve imaging of the brain's nucleus tractus solitarii (NTS) area, a brainstem structure thought to be involved in emotion regulation and in modulating the activity of various brain regions. Located deep in the brain and surrounded by regions critically involved in vital functions, the NTS has been difficult to observe directly.

"Previously, some approaches involved removing the cerebellum to access the NTS, but this posed a major limitation: the cerebellum is a motor coordination center and has also been recognized as important for emotional regulation," commented team member Masakazu Agetsuma.

"Therefore a method to observe the NTS while preserving cerebellar function has been needed."

The project's D-PSCAN solution involves an implantable double-microprism assembly, with a pair of 2-millimeter right-angle glass microprisms bonded together and a cover glass window at the surface-end position of the imaging window.

The complete double-prism assembly is implanted between the cerebellum and the brainstem of a mouse subject. Two-photon wide-field imaging of neural activity in the NTS can then be carried out via the two-prism window, using suitable calcium indicators.

Advances in mental health and well-being

In trials, the project used D-PSCAN to investigate the NTS's response to electrical stimulation of the vagus nerve conveying signals from internal organs to the NTS, observing the specific thresholds of vagus nerve stimulation intensity required to elicit neural responses.

Vagus nerve stimulation is already a clinical technique used as a therapy for drug-resistant epilepsy and is currently under investigation as a treatment for depression and other psychiatric and neurological disorders. An improved understanding of how different stimulation parameters cause patterns of neural activation, sensitization or inhibition could be valuable in developing new treatment regimes.

D-PSCAN imaging may also have an impact beyond the study of emotion regulation, since the NTS receives input from various organs including the heart and gut, and is involved in diverse functions such as appetite regulation, energy metabolism, and gut microbiota.

An in vivo imaging platform able to visualize NTS activity will allow researchers to better understand these and related complex interactions in this inaccessible area of the brain.

"The brain-body interaction plays a critical role in emotion regulation, and gaining a deeper understanding of this function is expected to contribute both to the treatment of neuropsychiatric disorders and to the advancement of mental health and well-being," commented Agetsuma.

"The D-PSCAN can offer a new approach to elucidate brain–body–mind interactions, and represents a valuable research tool for basic neuroscience to clinical applications."