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The Gist of It:
    My research has focused on 1) creating new connections in the brain to facilitate natural learning beyond inherent abilities, and 2) directly implanting new skills into the brain, and/or deleting existing skills. The former has involved tissue & materials engineering, while the latter has involved electrophysiological 'programming' and pharmacological manipulation of the neural connections which store 'muscle memories' in the brain. An overview of my work in these areas can be seen in the figures at the bottom of the page.

I. Creating Artificial Synesthesia Connections:
The brain's long distance connections ('white matter') are thouight to perform a fundamental role in the differences between cognitive abilities between species. These connections cannot be as easily modified by experience as shorter, more local connections ('grey matter'). Because of this, the engineering of white matter must instead rely on the physical creation of new connections via tissue engineering. Our studies involving the creation of artificial white matter connections via both 1) the creation of hydrogel tunnels embedded with dissociated neurons and 2) the grafting of degenerated peripheral nerves into brain tissue. Peripheral nerves grafted between seperate regions of the sensory cortex facilitate growth of novel axonal connectivity between these regions, creating a synesthetic effect (hand sensory region responding equaly well to whisker stimulation).

II. Programming New 'Muscle Memories':
The learning of new 'muscle memories' takes a great deal of time and effort and can therefore be limited more by behavioral factors than brain circuit capabilities and capacities. Muscle memories are refered to as sensorimotor memories in the neurobiology field. This is because they all involve first a sensing of ones environment and then an appropriate reaction to that sensory information. To advance the possibility of being able to instantaneously program new skills directly into the brain we attempted to modulate the weights of existing synaptic connections between the sensory (input) and motor (output) cortex. Using patterns of electrical microstimulation in both brain regions we successfully enhanced the strength of connectivity between specific, localized regions of the sensory and motor cortex. This is the first time that such an artificial manipulation of synaptic strength between the sensory and motor cortex has been shown. Future studies will acertain the degree to which these induced changes result in behavioral correlates.     

III. Deleting Existing 'Muscle Memories' & Sensory Maps:
In order to program new memories into the brain it may be useful in the future to delete existing memories, in order to free up limited neural real estate. We performed studies using ZIP, a drug which interferes with a protein thought to be highly involved in the storage of memories. ZIP deleted recently learned, and distantly learned sensorimotor memories, but allowed normal relearning of these memories afterwards, suggesting that no damage was done to the brain. In electrophysiological experiments it was observed that ZIP disrupted both natural response properties of the sensory cortex as well as sensory map boundaries.
Figure Legend:

I. Hydrogel Conduit: A) Enhanced photograph of the hydrogel tunnel and embedded neurons after being cultured for 3 days, allowing axonal growth to occur along the entire length of the tube. B) Bar graph showing consistency of dymensions in synthesized hydrogel tunnels. Peripheral Nerve Conduit: A) Cartoon showing harvesting of peripheral nerve and grafting into the cortex. B) Peri-stimulus time histograms showing responses to whisker and forelimb stimulation within a region of the sensory cortex normally responsive to only forelimb responses. C) Flourescence photos showing labeling by DiI in the cortex (DiI was applied to the surficial end of a grafted peripheral nerve), indicating functional integration of the graft with the host tissue.

II. Magnitudes of neural responses at different distances from the motor cortex neurons subjected to electrical microstimulation programming. The single peak at right indicates a desired localized effect of programming with little to no effect on neighboring, unprogrammed regions.

III. A) The effect of ZIP on magnitudes of neural responses within a region of sensory cortex naturally responsive to hindlimb stimulation. The red 'ghost' indicates pre-injection magnitudes and allows visualization of decreasing responses in the ZIP injected hemisphere over time. B) A model of response magnitude desynchronization in the injected vs. non-injected hemisphere following ZIP injection.