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The Journal of Neuroscience, July 9, 2003, 23(14):6123-6131

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Inhibitory But Not Excitatory Cortical Neurons Require Presynaptic Brain-Derived Neurotrophic Factor for Dendritic Development, as Revealed by Chimera Cell Culture

Keigo Kohara,^1,2 Akihiko Kitamura,^1,2 Naoki Adachi,^1,2 Megumi Nishida,^1,2 Chiaki Itami,³ Shun Nakamura,³ and Tadaharu Tsumoto^1,2

¹Division of Neurophysiology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan, ²Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi 442-0012, Japan, and ³Division of Biochemistry and Cellular Biology, National Institute of Neuroscience, Kodaira 187-8502, Japan

To address questions of whether endogenous BDNF acts differentially on inhibitory and excitatory neurons, and through what routes, we used chimera culture of cerebral cortical neurons derived from BDNF-/- mice and another type of transgenic mice that express green fluorescence protein and BDNF. Presynaptic BDNF transferred to both types of neurons, GABA-synthesizing enzyme-positive and -negative neurons. The latter neurons were confirmed to be glutamatergic with immunocytochemistry. Dendritic development of the former inhibitory neurons was promoted by endogenous BDNF transferred from presynaptic, excitatory neurons. In contrast, dendritic development of excitatory neurons was not related to the presence or absence of presynaptic BDNF, suggesting that BDNF acts on inhibitory neurons through an anterograde, transsynaptic route so as to promote dendritic development, whereas this is not the case in excitatory neurons.

Key words: neurotrophin; brain-derived neurotrophic factor; dendritic growth; inhibitory neuron; visual cortex; chimera cell culture; green fluorescence protein

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Received Oct. 9, 2002; revised Apr. 21, 2003; accepted Apr. 23, 2003.

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