9728742 LI During the development of many sensory systems in vertebrates, the sensory periphery (e.g. the body surface, or retina of the eye) must become properly mapped in the central nervous system. Previous research has shown that some aspects of this mapping depend on neural activity to match up the central maps to individual differences in the sensory periphery. Dr. Li's research is to understand how neural activity regulates the formation of specific synaptic connections in brain maps that represent the whiskers on a mouse's face . In the past, Dr. Li and his colleagues developed a line of transgenic mice without NMDA receptors (a subtype of glutamate receptor in the brain) to study activity-dependent synaptic refinement. Their work on the whisker-to-barrel, or trigeminal, sensory system has shown that the formation of the whisker-related neural maps in brainstem trigeminal nuclei requires NMDA receptor activity. However, it has been unsettled whether the development of whisker-related patterns requires NMDA receptor activation at the higher levels (thalamus and cerebral cortex) along the trigeminal neuraxis. In order to resolve this issue, Dr. Li and his colleagues will use the Cre/LoxP technique to delete one subtype of NMDA receptor in the developing cortex. They have recently created a line of transgenic mice that can inactivate tagged genes specifically in the developing cerebral cortex by the restricted expression of a bacterial recombinase enzyme (cre). When crossed with other transgenic mice in which the NR2B subunit of the NMDA receptor has been inserted between two LoxP sites, the cre-mediated recombination will delete the NR1/NR2B subtype of NMDA receptors in the cerebral cortex. They will then study the development and plasticity of whisker-related neuronal patterns in the cerebral cortex. In collaboration with other researchers, Dr. Li's group uses gene targeting technology, axonal tracing, whole-cell patch clamp and extracellular recording techniques combined wi th histochemical detection methods to reveal the anatomical and functional organization of the whisker-to-barrel sensory system in these genetically altered mice. This multidisciplinary research should lead to a comprehensive understanding of the molecular and cellular mechanisms of cortical development and plasticity.
