SHIMIZU K Lab
医薬理工学環 Graduate School of Pharma-Medical Sciences
理工学研究科 Graduate School of Science and Engineering
About
Research Overview
Various physiological functions of living organisms are rhythmically controlled by our internal biological clock (circadian clock) and undergo diurnal changes. In our laboratory, we are conducting research at multiple levels, from molecules to behavior, to clarify the mechanism by which higher brain functions such as memory formation and emotional control are controlled by the circadian clock. Currently, we are mainly conducting the following research:
- Elucidation of the molecular mechanisms of time-dependent changes in memory, emotion, and olfaction.
- Visualization and application of changes in synapses accompanying changes in brain function.
- Mechanism of action of novel neurosteroids.
Circadian rhythm of learning and memory effect
The circadian clock controls the performance of long-term learning and memory. When the circadian clock center is physically destroyed or when the hippocampal clock molecule (Bmal1) is deleted, the performance of long-term learning and memory declines and the animal is unable to remember much at any time. In this case, short-term memory is not affected. We have revealed that circadian changes in SCOP molecules in the hippocampus regulate the K-Ras-ERK/MAPK-CREB pathway, thereby generating circadian rhythms in long-term memory (left figure, Shimizu et al. Nat. Commun). We have also found that SCOP molecules control the efficiency of memory learning in Japanese macaques and play an important role in generating the diurnal rhythm of memory learning performance (Shimizu et al. Mol. Brain). We have found that the diurnal rhythm of memory learning performance and the mechanism of SCOP dependency are likely to be common to mammals.
Circadian rhythm of emotion
We found that anxiety-like behavior in mice also has a circadian rhythm and depends on the circadian clock and the changes in SCOP amount in the amygdala (BLA) that are controlled by the circadian clock (Nakano et al. Sci. Rep). Not only anxiety-like behavior, but also depression-like behavior rhythms were observed, and we are currently investigating the responsible brain regions and molecular mechanisms.
Neurosteroids have a beneficial effect on memory maintenance
Neurosteroids are a general term for steroid hormones synthesized from cholesterol in the brain. We have revealed that the new neurosteroids 7α-hydroxypregnenolone (7α-OH-Preg) and 7α-hydroxydehydroepiandrosterone (7α-OH-DHEA) contribute to the long-term maintenance of spatial memory through remodeling of hippocampal neural spines (Maehata et al. iScience). They do not affect learning ability or short-term memory, but only the ability to maintain memory for a long time. Elucidating the mechanism of action of these neurosteroids may lead to the development of methods to maintain memory learning.
Our laboratory is looking for people who are interested in our research, including circadian rhythms of learning and memory, emotions, and some higher brain functions.
Kimiko Shimizu
Ph.D. (Science)
Professor,
Organization for International Education and Exchange
(International IR/Security Export Control Division),
University of Toyama