Educational Activities

School: Biochemistry of Cell Responsiveness

Research Activities

Neural Plasticity -Adult Hippocampal Neurogenesis (2001-Present):
New neurons are continuously generated in the subgranular zone of the hippocampal dentate gyrus thoughout adulthood and are involved in some hippocampal-dependent learning and memory. Adult hippocampal neurogenesis is enhanced in particular physiological conditions (enriched environments, learning, exercise, etc.) and pathological conditions (epilepsy, ischemic stroke, etc.). We focus on the activity-dependent regulation of adult neurogenesis, and we have discovered the activation of hippocampal stem/progenitor cells by typical hippocampal network activity, theta oscillations. The biochemical mechanism responsible for this activity-dependent regulation has been clarified. Since, the synaptic plasticity of new granular neurons is higher than for old granular neurons; activity-dependent enhanced neurogenesis perhaps contributes to the dynamic reorganization of the hippocampal circuit.

Literature

1) Tozuka Y; Fukuda S; Namba T; Seki T; Hisatsune T "GABAergic excitation promotes neuronal differentiation in adult hippocampal progenitor cells" Neuron, 47, 803-815 (2005)
2) Fukuda S; Kato F; Tozuka Y; Yamaguchi M; Miyamoto Y; Hisatsune T "Two distinct subpopulations of nestin-positive cells in adult mouse dentate gyrus" J. Neurosci., 23, 9357-9366 (2003)
3) Koketsu D; Mikami A; Miyamoto Y; Hisatsune T "Non-renewal of neurons in the cerebral neocortex of adult Macaque monkeys" J. Neurosci., 23, 937-942 (2003)

Future Plan

Our laboratory has as its mission the development of therapeutic regenerative applications for neurodegenerative disorders, psychiatric diseases, and dementia. Worldwide, the number of people with dementia is steadily rising. In general, people think that once such neurological symptoms appear the diseases can not be cured. However, in the late 20th century, neuroscientists discovered several cellular potentials for neural circuit repair after damage. Adult neurogenesis is one of the promising candidates to drive neural repair since we can modulate the rate of neurogenesis by drugs or simply by a change in lifestyle. Other candidates would come from the plasticity of the neural circuit. We know the formation of new synapses is taking place all around the cerebral cortex, even in the adult stage. Axon fibers penetrating into large and wide white matters of human brains are also flexible. Full maturation of human white matter occurs during the 50s. Even if axonal fibers are damaged, our brains possess self-repairing mechanisms, such as remyelination or re-sprouting of axonal fibers. When we image a clear scientific goal, we will get it in future.

Messages to Students

I have a dream. For over 100 years, many neuroscientists have tried to understand how our brain works. Although there have been many discoveries and dozens of Nobel laureates have come from this field, much work remains and many of the principle driving our brains are still missing. We can not keep our own brains under perfect control?the brain itself seems like another organism living in our skull. People in a positive mood think well and sometimes create new things, but people in negative mood can not concentrate and often feel psychiatric stress. I think the clues to solving this irritating question will be something between mind (soft ware) and brain (hard ware). I may be too old to obtain new brain principal, but this represents a big chance for young students to develop new theories to understand our brains. I promise this discovery will greatly refresh you.

URL

http://hisatsune-lab.k.u-tokyo.ac.jp/en/news-2/