title: Adaptive reorganization of retinogeniculate axon terminals in dorsal lateral geniculate nucleus following experimental mild traumatic brain injury.
abstract: The pathologic process in traumatic brain injury marked by delayed axonal loss, known as diffuse axonal injury (DAI), leads to partial deafferentation of neurons downstream of injured axons. This process is linked to persistent visual dysfunction following mild traumatic brain injury (mTBI), however, examination of deafferentation in humans is impossible with current technology. To investigate potential reorganization in the visual system following mTBI, we utilized the central fluid percussion injury (cFPI) mouse model of mTBI. We report that in the optic nerve of adult male C57BL/6J mice, axonal projections of retinal ganglion cells (RGCs) to their downstream thalamic target, dorsal lateral geniculate nucleus (dLGN), undergo DAI followed by scattered, widespread axon terminals loss within the dLGN at 4days post-injury. However, at 10days post-injury, significant reorganization of RGC axon terminals was found, suggestive of an adaptive neuroplastic response. While these changes persisted at 20days post-injury, the RGC axon terminal distribution did not recovery fully to sham-injury levels. Our studies also revealed that following DAI, the segregation of axon terminals from ipsilateral and contralateral eye projections remained consistent with normal adult mouse distribution. Lastly, our examination of the shell and core of dLGN suggested that different RGC subpopulations may vary in their susceptibility to injury or in their contribution to reorganization following injury. Collectively, these findings support the premise that subcortical axon terminal reorganization may contribute to recovery following mTBI, and that different neural phenotypes may vary in their contribution to this reorganization despite exposure to the same injury.
authors.affiliation: Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, USA. Electronic address: vpatel4@vcu.edu.
authors.forename: Vishal C
authors.initials: VC
authors.lastname: Patel
authors.affiliation: Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, USA. Electronic address: cjurgens@vcu.edu.
authors.forename: Christopher W D
authors.initials: CWD
authors.lastname: Jurgens
authors.affiliation: Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, USA. Electronic address: tekrahe@gmail.com.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Krahe
authors.affiliation: Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, USA. Electronic address: john.povlishock@vcuhealth.org.
authors.forename: John T
authors.initials: JT
authors.lastname: Povlishock
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000473:pathology*; D002772:Cholera Toxin / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005829:Geniculate Bodies / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology*; D012160:Retina / Q000473:pathology*; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism; D014795:Visual Pathways / Q000503:physiopathology*
chemical_list: D050599:Vesicular Glutamate Transport Protein 2; D002772:Cholera Toxin
keywords: Axon terminals; Diffuse axonal injury; Lateral geniculate bodies; Neuronal plasticity; Traumatic brain injury; Visual system