(Applicant?s Abstract) Repairing nervous system injury represents a major challenge in contemporary neuroscience. The ability of networks of neurons to reorganize after de-afferentiation is a general organizing principle of the nervous system that has been demonstrated by single cell recordings in numerous areas, including visual, motor, and somatosensory cortex. In the proposed project, the applicant will use high field functional magnetic resonance (fMRI) to study the process of reorganization triggered by an acute retinal scotoma in the visual cortex of human and non-human primates (macaca mulatta).
Specific aim one will generate and validate a high field fMRI paradigm for the study of neural plasticity in macaque visual cortex after induction of a homonymous retinal scotoma. This will test the hypothesis that fMRI can be used to monitor in vivo the reorganization seen in macaque visual cortex after retinal injury.
Specific aim two will compare the extent, rate and temporal order of reorganization in the hierarchy of visual areas downstream from the homonymous retinal lesion to test the hypothesis that extrastriate areas reorganized in a serial fashion, i.e. lower areas precede higher ones.
Specific aim three will apply the experimental paradigm established in aims one and two to test whether brain derived neurotrophic factor (BDNF) can enhance reorganization in macaque visual cortex as hypothesized by Obata. et al., [Cerebral Cortex 9, 238-48, ?99].
Specific aim four will map reorganization in the visual cortex of adult humans with ischemic optic neuropathy or branch retinal artery occlusion. This will test the hypothesis that adult human visual cortex reorganizes after retinal injury. By comparing the pattern of reorganization seen in macaques and humans, this will establish the validity of macaque fMRI as a model for the study of neural plasticity in the human. The candidate?s long term goal as a neurologist specializing in stroke is to pursue an academic career studying mechanisms of stroke recovery. Combining training in human fMRI with training in primate fMRI and electrophysiology is highly relevant. The development of an fMRI method to monitor reorganization in vivo in macaque visual cortex puts this process under experimental control, which is not possible in the human. The proposed paradigm will provide a reliable, noninvasive means of gauging the global effect of experimental manipulations on neuronal recovery after injury or sensory deprivation. Future directions of research include studying the effects that pharmacologic agents or rehabilitative approaches have on cortical reorganization and functional recovery after nervous system injury.
