SPINAL CORD INJURY
Axons in the adult central nervous system (CNS) fail to regenerate after spinal cord injury (SCI), therefore patients with severe SCI remain insensate and paralyzed below the level of the injury. Despite the lack of long distance axon regeneration, partial spontaneous recovery of function is observed in human SCI patients and animal SCI models. Structural plasticity of intact cortical, corticofugal, and spinal circuitry has been suggested to drive this phenomenon. However, the molecular mechanisms underlying functional plasticity of intact circuits remain unknown.
OUR MISSION
Research in the Cafferty lab focuses on the capacity of intact CNS circuitry to undergo structural plasticity to drive restoration of function post injury. Using transcriptional profiling, genetics, proteomics, physiology, in vivo neuro-surgical trauma, behavioral studies, biochemistry, tissue culture and chronic two-photon and mesoscale in vivo imaging methodology, we seek to identify and exploit the molecular mechanisms that drive structural plasticity in intact CNS neurons and develop new tools with which to specifically study these pathways to design novel therapies to treat injury and disease of the CNS.
OUR MODEL
Our current studies focus on central motor pathways, specifically the corticospinal tract (CST). The CST forms an integral part of the motor apparatus in mammals that controls fine motor movement and regulates sensory input. CST somata reside in layer 5b of primary motor cortex (M1) and project axons to major motor centers including the Red Nucleus, brainstem and in every spinal segment and Rexed’s lamina. The CST presents a unique opportunity to explore the molecular mechanisms necessary for axon growth after injury as it transitions early postnatally (P 0-10) from a growth competent mode, to an adult growth incompetent mode (P56 and beyond). In addition, previous work from our lab and others has shown that intact CST neurons sprout into denervated spinal regions after a unilateral pyramidotomy (uPyX), and that genetic, pharmacological and activity driven interventions that enhance contralateral sprouting result in increased functional recovery. Emerging data has also shown that rehabilitative training can elevate CST function after injury. Thus, the CST maintains the potential to undergo functional plasticity after injury (summarized in the schematic below).
The corticospinal tract (orange) is shown with somata in layer 5 of motor cortex. Different phases of CST terminal patterning through developmental epochs is shown, notionally each of these phases is determined by a unique set of transcriptional machinery. Specific programs of growth may be reactivated after partial injury (PyX). Ongoing experiments plan to interrogate these temporally specific gene expression patterns to ultimately exploit them to restore function after chronic spinal cord injury.