In-vivo Tracing of Vagal Projections in the Brain with Manganese Enhanced Magnetic Resonance Imaging
Current challenges in neuronal tract tracing include sacrificing the animal, detailed sectioning of the brain, and cumbersome reconstruction of slices to gather information, which are very tedious, time consuming, and have low-throughput. In this regard, Manganese-enhanced Magnetic Resonance Imaging (MEMRI) has been an emerging methodology for fiber tract tracing in vivo. The manganese ion (Mn2+) is paramagnetic and is analogous to calcium ions (Ca2+), which allows it to enter excitable cells through voltage-gated calcium channels, thereby reporting cellular activity in T1-weighted MR images. Moreover, once the Mn2+enters the cell, it will move along the axon by microtubules, release at the synapse, and then uptake by post-synaptic neurons, hence revealing the pathway of Mn2+ transportation. While most MEMRI neuronal tracing studies have focused on mapping circuitries within the brain, MEMRI has rarely been applied to trace peripheral nerve projections into the brain.
In this thesis, I will propose the use of MEMRI to trace vagal nerve projections into the central nervous system by showing enhancement of neuronal pathways with an optimized protocol. This protocol demonstrates in vivo monitoring of manganese transport into the brain from the nodose ganglion and shows how the enhancement in MR images can be promoted with vagus nerve stimulation (VNS). Additionally, I will present preliminary findings, for the very first time, that show the downstream projection of the sympathetic pathway from the brainstem. In sum, the technique presented in this thesis will shed light on the use of MEMRI to study the functional results of using clinically-based VNS settings