The dawn of excitatory amino acid research in Japan. The pioneering work by Professor Takashi Hayashi.

The excitatory action of glutamate and aspartate upon direct application to the motor cortex of dogs was first reported in 1952 by Takashi Hayashi, Keio University School of Medicine, Tokyo. Although this investigation had been performed in the early 1940s during the Second World War, the publication in English was delayed in the difficult post-war circumstances. When sodium glutamate was applied to the exposed motor cortex in 1-2 mol (not mmol) concentrations, the convulsions of a clonic type were produced with very short latent periods. He injected glutamate free-hand by using an intradermic syringe for humans. Stimulation by glutamate was solely effective in the grey matter. If entered into the white matter, it had no motor effects. When Hayashi undertook this investigation, glutamate was not known to exist in a high concentration in the brain. Hayashi proposed the physiological role of glutamate in the brain excitation, and hypothesized that glutamate might be inactive in the brain tissue, probably bound to protein, and that upon release from protein the excitatory action might be expressed. The electrical stimulation of the cortex was suggested to induce the release of glutamate from protein.