Rewiring cortex using inhibitory neuron transplantation Childhood experiences shape our perceptions and behaviors. The same experiences as adults have little effect. Underlying the perceptual and behavioral malleability of youth is the pronounced capacity of the young brain to be rewired. One class of neurons, inhibitory interneurons, has been shown to play an active role in promoting the plasticity of the juvenile visual cortex. We recently discovered that transplantation of inhibitory interneurons reactivates plasticity in the visual cortex. In this proposal, we will use inhibitory neuron transplantation to gain insight into the mechanisms of cortical plasticity. We found previously that transplanted inhibitory neurons made direct synaptic connections with the host brain. We propose using in vivo calcium imaging of visual responses and in vivo optogenetic stimulation to study the input and output connections made by transplanted inhibitory neurons with cells in the host visual cortex. Our hypothesis is that transplanted cells add a pattern of variable inhibition o the host brain that makes existing connections in the visual cortex quicker to adapt to changes in sensory experience. We also propose to investigate whether the transplantation of inhibitory neurons reactivates plasticity when implanted into the fully adult brain. Therapeutic rewiring of adult cortex using transplantation would represent an entirely new avenue for reversing brain damage. Eventually, this research program may identify novel molecular interventions that promote brain plasticity by reactivating dormant developmental programs in endogenous inhibitory neurons.
