Cross-modal plasticity after the loss of vision at two early developmental ages in the posterior parietal cortex: Adult connections, cortical function and behavior.

The mammalian neocortex has a remarkable ability to change over a lifetime, particularly during early development. The development of the cortex, sensory fields and their connections are dependent on the incoming sensory inputs from the sensory receptors in the periphery. This early, spontaneous sensory input, together with sensory experience from the environment shapes the neocortex to generate optimal behavior. We know from studies in humans and rodents that early loss of vision leads to massive changes in the brain; what would normally be visual and posterior parietal cortical areas contains neurons that respond only to somatosensory and auditory stimulation. This reorganized occipital cortex receives ectopic input from thalamic nuclei and cortical fields associated with somatosensory and auditory processing. The current proposal addresses several fundamental questions raised by these previous findings: 1) How does the age of onset of blindness differentially impact cortical connectivity of the medial and lateral divisions of the posterior parietal cortex (PPCL and PPCM)? 2) What are the single-neuron response properties in PPCM and PPCL, and does the age of blindness onset impact these properties? 3) What is the relationship between functional and anatomical changes PPCL and PPCM and the compensatory behaviors mediated by the spared sensory systems? In these experiments, bilateral enucleations in the highly altricial short-tailed opossum (Monodelphis domestica) will be made at two developmental milestones: 1) Prior to the onset of spontaneous activity in the retina, before retinal geniculate axons reach the thalamus, and before thalamocortical axons have innervated the neocortex; 2) When spontaneous activity in the retina is ongoing and retinogeniculate and thalamocortical axons have innervated their targets. Following enucleations, animals will be assessed at two time points allowing us to directly assess the impacts of blindness at important developmental milestones. These data can direct therapeutic interventions to compensate for the loss of vision that targets higher-order cortical function.