Spinal serotonin in cerebral palsy

The goal of the proposed work is to identify physiological deficits in spinal circuits that develop following fetal hypoxia-ischemia (H-I) insult in rabbit kits. This H-I model of cerebral palsy replicates an important feature of the disease in human patients: hypertonicity of distal limbs resulting from altered descending corticospinal and rubrospinal inputs. Experiments on the in vitro rabbit spinal cord will determine, at two developmental time points, the progression of intrinsic excitability (persistent inward currents and other membrane properties) and extrinsic excitability (response to bath application of 5HT, as well as their response to stimulation of both local spinal circuits and descending tracts) in control, sham and affected rabbit kits. The three data sets are then related quantitatively, to pinpoint targets for pharmacological restoration of normal function, and the window in which treatments could be best applied.