Systems Neuropharmacology

detail13 Yasunori Hayashi, M.D., Ph.D.Professor btn

We daily form new memories. Surprisingly, once we remember something, we can recall them even after decades. What is the mechanism that keeps these memories in our brain?
We are particularly interested in hippocampus, a brain region involved in initial formation of memory. In hippocampus, short intense stimuli potentiate synaptic responses over a long period of time, a phenomenon known as long-term potentiation (LTP). We consider that LTP is a cellular counterpart of memory and are trying to elucidate the molecular mechanism of this phenomenon.

Research and Education

We are particularly interested in a brain region called hippocampus. In humans and animals with hippocampal damage, no new memories are formed. This indicates that hippocampus is necessary for the formation of new memories.

About 40 years ago, Bliss and Lømo discovered an interesting phenomenon in the hippocampus. They found that synaptic responses in the hippocampus is enhanced over the long period of time by a short but intense stimulation, which is now known as long-term potentiation (LTP). LTP is thought to be a cellular phenomenon of memory from several lines of evidence. For example, a drug that inhibits LTP can impair formation of memory. Also, memory induction enhances synaptic responses in a similar way to LTP.

Using LTP as a cellular model, we are trying to elucidate the molecular mechanism of memory. To this end, we are using various techniques such as molecular biology, electrophysiology, animal behavioral experiments, and imaging to advance our research.


Actin polymerization and expansion of dendritic spineFigure 1. Visualization of synaptic plasticity processes.
FRET was used to visualize the actin polymerization state. LTP was induced at the arrow.
Scale bar is 0.5 µm and time stamp in minutes.

mouse_on_trackballFigure 2. Visualization of formation of cell assembly during memory formation in hippocampus.
The mouse runs on a Styrofoam sphere and a virtual reality space updated as it moves.
Neuronal activity in the hippocampus is observed using a two-photon microscopy.

Recent Publications

  1. Masaaki Sato, Kotaro Mizuta, Tanvir Islam, Masako Kawano, Yukiko Sekine, Takashi Takekawa, Daniel Gomez-Dominguez, Alexander Schmidt, Fred Wolf, Karam Kim, Hiroshi Yamakawa, Masamichi Ohkura, Min Goo Lee, Tomoki Fukai, Junichi Nakai, Yasunori Hayashi
    Distinct Mechanisms of Over-Representation of Landmarks and Rewards in the Hippocampus. Cell Rep: 2020, 32(1);107864
  2. Takeo Saneyoshi, Hitomi Matsuno, Akio Suzuki, Hideji Murakoshi, Nathan G Hedrick, Emily Agnello, Rory O’Connell, Margaret M Stratton, Ryohei Yasuda, Yasunori Hayashi
    Reciprocal Activation within a Kinase-Effector Complex Underlying Persistence of Structural LTP. Neuron: 2019, 102(6);1199-1210.e6
  3. Karam Kim, Gurpreet Lakhanpal, Hsiangmin E Lu, Mustafa Khan, Akio Suzuki, Mariko Kato Hayashi, Radhakrishnan Narayanan, Thomas T Luyben, Tomoki Matsuda, Takeharu Nagai, Thomas A Blanpied, Yasunori Hayashi, Kenichi Okamoto
    A Temporary Gating of Actin Remodeling during Synaptic Plasticity Consists of the Interplay between the Kinase and Structural Functions of CaMKII. 
Neuron: 2015, 87(4);813-26
  4. Tomohisa Hosokawa, Dai Mitsushima, Rina Kaneko, Yasunori Hayashi
    Stoichiometry and phosphoisotypes of hippocampal AMPA-type glutamate receptor phosphorylation. 
Neuron: 2015, 85(1);60-7
  5. Miquel Bosch, Jorge Castro, Takeo Saneyoshi, Hitomi Matsuno, Mriganka Sur, Yasunori Hayashi
    Structural and molecular remodeling of dendritic spine substructures during long-term potentiation. 
Neuron: 2014, 82(2);444-59

Systems Neuropharmacology

Professor: Yasunori Hayashi
Associate Professor: Takeo Saneyoshi
Assistant Professor: Kotaro Mizuta
Program-Specific Assistant Professor: Akihiro Goto