The PI has established a Neurobiology Laboratory in the Graduate Institute of Anatomy and Cell Biology, National Taiwan University and explored the property of the cortical subplate and the function of CTGF, a prominent marker for subplate neurons. We characterized the electrophysiological and morphological properties of subplate neurons in the developing rat brains and suggested a transient role for thalamocortical circuit formation. Since cortical subplate is innervated by serotonergic fibers, we examined the functional and structural defects following early disruption of the serotonergic system. Altered subplate cytoarchitecture and dysregulated serotonergic system are linked with various mental disorders. We therefore characterized the neuronal deficits in rodent models of developmental neuropsychiatric diseases such as mental retardation, sensory deprivation, autism, schizophrenia, epilepsy and muscular dystrophy.
Connective tissue growth factor (CTGF) is expressed in the subplate or layer VIb neurons as well as the external tufted cells in the olfactory bulb and excitatory neurons in the endopiriform nucleus. We have generated a gene knockout (FbCtgf KO) mouse model that Ctgf is conditionally removed from the excitatory neurons in the forebrain before its native expression. In the cerebral cortex of FbCtgf KO mice, the thickness of myelin sheath in the external capsule underneath the cortical subplate are reduced in FbCtgf KO mice, indicating a paracrine function of subplate-derived CTGF. Endopiriform nucleus has been noted as an epileptogenic site, we examined the seizure reaction and morphometric changes of brain cells following PTZ-induced seizure. We also characterized the olfactory phenotypes of FbCtgf KO mice.
Besides, we are interested in the role of microglia in the brain. We have characterized the morphology and status of microglia in LPS-treated mice, sleep-deprived adolescent and adult mice as well as a mouse model of traumatic brain injury.
Human brain tissue samples are valuable research resources and indispensable for the study of brain science. The PI is actively involved in the establishment of Brain Bank in Taiwan.
1. Yu IS, Chang HC, Chen KC, Lu YL, Shy HT, Chen CY, Lee KY, Lee LJ*. Genetic Elimination of connective tissue growth factor in the forebrain affects subplate neurons in the cortex and oligodendrocytes in the underlying white matter. Front Neuroanat. 2019, 13:16.
2. Tuan LH, Lee LJ*. Microglia-mediated synaptic pruning is impaired in sleep-deprived adolescent mice. Neurobiol Dis. 2019, 130:104517.
3. Baskaran R, Lai CC, Li WY, Tuan LH, Wang CC, Lee LJ, Liu CM, Hwu HG, Lee LJ*. Characterization of striatal phenotypes in heterozygous Disc1 mutant mice, a model of haploinsufficiency. J Comp Neurol. 2020 528:1157-1172.