DEVELOPMENT OF PHYSIOLOGICAL FUNCTION OF VISUAL CORTEX

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In this research project we attempted to elucidate a role of brain-derived neurotrophic factor (BDNF) in development of neuronal circuits of the cerebral cortex. In 2000 and 2001, we investigated a possible contribution of BDNF in formation of ocular dominance (OD) columns in kitten visual cortex, and found that BDNF expands the size of OD columns. Also, we found that BDNF is released from presynaptic neurons and transferred to postsynaptic neurons in an activity-dependent manner. In 2002 we studied a possible involvement of BDNF in long-term depression (LTD) of synaptic transmission in visual cortex. We found that BDNF, which was exogenously applied to visual cortical slices prevented prolonged, low-frequency stimulation (LFS) of afferents from inducing LTD at synapses of cortical layer II/III neurons. Also we found that in the more physiological in vivo condition, LFS did not induce LTD because of the presence of endogenous BDNF in visual cortex. In 2003 and 2004 we tested whether BDNF has any action on development of GABAergic, inhibitory neurons using neuron culture preparations or visual cortical slices of GAD67-GFP knock-in mice. We found that BDNF promotes morphological and functional development of postsynaptic, GABAergic neurons. Because GABAergic neurons cannot produce BDNF by themselves and thus depends on BDNF which is transferred from other excitatory neurons in an activity dependent manner, the dependency of development of immature neuronal circuits on neuronal activity is ascribable mostly if not all to the dependency of development of GABAergic neurons on BDNF.