SCI results in currentlyirreversible devastating functional impairments. Damaged axons fail to regenerate after SCI due to the inhibitory environment in the mature central nervous system (CNS) and the low intrinsic growth capacity of adult CNS neurons.Strategies designed to elevate the intrinsic growth capacity of damaged CNS or nullify the effects of environmental inhibitors either geneticallyor pharmacologically has led to encouraging but also incomplete axon re-growth and minimal functional restoration. Common to all clinical and experimental mild and severe SCI is the emergence of spontaneous recovery of function. This observation is at odds with the incapacity of damaged CNS axons to regenerate? An alternative to regeneration, localized growth or plasticity of intact axons may play an integral role in functional recovery after SCI. To fully realize the potential for intact circuitry to restore function after brain and spinal cord injury, research in the Cafferty lab is focused on three related areas utilizing a broad range of cutting-edge techniques.
Defining the molecular mechanisms driving functional plasticity after injury.
Identification of areas undergoing functional plasticity after injury.
Exploitation of the molecular mechanism driving plasticity to enhance functional recovery after brain and spinal cord injury.
1) Anatomical Origins of Functional Plasticity
Chronic in vivo mesoscale two-photon cortical and spinal microscopy in awake behaving mice allows us to observe how neuronal network connectivity and activity change during critical periods, learning, aging and injury. Genetically encoded calcium and voltage sensors restricted spatially (via viral delivery) or by cellular phenotype (via specific crelines) allows us to investigate how network activity is sculpted by normal and aberrant stimuli. Furthermore, structural changes (axonal, dendritic and dendritic spine) can be observed via pan neuronal (or restricted) expression of soluble or membrane specific fluorescent reporters.