The basis for neuronal dysfunction following inflammatory demyelination of the central nervous system (CNS) remains poorly understood. We characterized the network response to white matter injury in the anterior visual pathway using an experimental model of optic neuritis (ON), as ON is often an early manifestation of immune-mediated CNS demyelination in multiple sclerosis (MS). Optical intrinsic signal imaging was performed before and after the induction of ON in mice to measure changes in cortical network functional connectivity. We observed a greater loss of connectivity between homotopic visual cortices in ON mice compared to controls. Further, decreases in homotopic visual cortex connectivity were associated with visual acuity loss in ON mice. These results demonstrate that network connectivity changes resulting from ON can be modeled in an experimental murine system. Future studies will identify the mechanisms that cause neuronal dysfunction due to white matter injury seen in MS.
Bibliographical noteFunding Information:
We thank Kenneth Shindler, MD, PhD (The University of Pennsylvania) for input on ON assessment and Grant Baxter at Washington University in St. Louis for technical assistance. Funding: this work was supported by the National Institutes of Health (grant numbers R01NS083678 (GFW), R01NS0836780 (BMA), R01NR014449 (BMA), R01NR012907 (BMA), and R01NR012657 (BMA)).
- Functional connectivity
- Multiple sclerosis
- Optic neuritis
- Optical imaging
- Visual cortex