Memory Neuroscience

Members

Theme Leader :
Sho Kakizawa, Ph.D.

Keywords

memory, learning, functional compensation, plasticity, synapse, cerebellum, reactive oxygen species (ROS), nitric oxide (NO), calcium (Ca2+)

Major Research Titles

  1. Signaling Mechanisms of Learning & Memory / Synaptic Plasticity
  2. Cellular and Molecular Mechanisms of Brain Function Decline
  3. Functional Compensation of the Cerebellum: Mechanisms and Influencing Factors

Profile

Addressing the decline in brain function caused by conditions like dementia and neurodegenerative diseases is a critical challenge in our aging society. While brain functions remain relatively stable after maturation, they decline with aging, trauma, or neurodegenerative diseases. However, recovery of brain function has also been observed in younger individuals. Understanding the mechanisms behind the "maintenance," "decline," and "recovery" of brain function, as well as the factors influencing these processes, such as drugs, dietary components, exercise, and enriched environments, is crucial for developing effective interventions.

Our research focuses on the cerebellum, a brain region with relatively simple and organized neural circuits, to uncover mechanisms that maintain, impair, or recover brain function. Through this research, we aim to develop novel methods to control brain function, ultimately laying the groundwork for preventing or treating brain function decline, including cognitive dysfunction in humans.

  1. Signaling Mechanisms of Learning & Memory / Synaptic Plasticity
    Memory and learning are essential for rational behavior and avoiding danger. A decline in these abilities significan    tly impacts quality of life (QOL). Synaptic plasticity, the ability of synapses to change and adapt, serves as a cellular basis for memory and learning. Despite extensive research, many aspects of the molecular mechanisms underlying the persistence of synaptic plasticity remain unclear. Our research focuses on redox signaling (e.g. reactive oxygen species (ROS) and nitric oxide (NO)) and intracellular calcium release systems as signaling molecules presumed to be involved in learning & memory / synaptic plasticity. Additionally, we are investigating the processes of memory retention and decay following learning, as well as identifying factors that influence these processes.
  2. Cellular and Molecular Mechanisms of Brain Function Decline
    Aging-related decline in brain function is observed in various forms of memory and learning, including cerebellar     motor learning. Although some mechanisms have been uncovered, many remain unclear. Our previous research has demonstrated age-related inhibition of long-term potentiation (LTP), a cellular basis of learning and memory, in cerebellar synapses. We continue to investigate the molecular and cellular mechanisms of this decline, as well as identifying factors influencing it.
  3. Functional Compensation of the Cerebellum: Mechanisms and Influencing Factors
    Recent studies show that the cerebellum is involved in not only motor functions but also in cognitive and emotional functions. The cerebellum exhibits remarkable recovery potential after injury, mediated by functional compensation in undamaged regions. By elucidating the mechanisms behind cognitive recovery in the cerebellum following brain injury, identifying recovery-promoting factors, and understanding their modes of action, we aim to establish methods to facilitate brain recovery, with the ultimate goal of applying these findings to humans.

References

(Selected Publications)

1. Original Papers

  1. Kakizawa S. Assessment of retention and attenuation of motor-learning memory by repeated rotor-rod analyses. Scientific Reports 14, 31003, 2024.
  2. Kakizawa S, Arasaki T, Yoshida A, Sato A, Takino Y, Ishigami A, Akaike T, Yanai S, Endo S. Essential role of ROS - 8-Nitro-cGMP signaling in long-term memory of motor learning and cerebellar synaptic plasticity. Redox Biol 70, 103053, 2024.
  3. Kakizawa S, Kishimoto Y, Yamamoto S, Onga K, Yasuda K, Miyamoto Y, Watanabe M, Sakai R, Mori N. Functional maintenance of calcium store by ShcB adaptor protein in cerebellar Purkinje cells. Scientific Reports 10, 14475, 2020.
  4. Mikami Y, Kanemaru K, Okubo Y, Nakaune T, Suzuki J, Shibata K, Sugiyama H, Koyama R, Murayama T, Ito A, Yamazawa T, Ikegaya Y, Sakurai T, Saito N, Kakizawa S, Iino M. Nitric Oxide-induced Activation of the Type 1 Ryanodine Receptor Is Critical for Epileptic Seizure-induced Neuronal Cell Death. EBioMedicine 11, 253-261, 2016.
  5. Kakizawa S, Shibazaki M, Mori N. Protein oxidation inhibits NO-mediated signaling pathway for synaptic plasticity. Neurobiol. Aging 33, 535-545, 2012.
  6. Kakizawa S, Yamazawa T, Chen Y, Ito A, Murayama T, Oyamada H, Kurebayashi N, Sato O, Watanabe M, Mori N, Oguchi K, Sakurai T, Takeshima H, Saito N, Iino M. Nitric oxide-induced calcium release via ryanodine receptors regulates neuronal function. EMBO J. 31, 417-428, 2012.
  7. Kakizawa S, Kishimoto Y, Hashimoto K, Miyazaki T, Furutani K, Shimizu H, Fukaya M, Nishi M, Sakagami H, Ikeda A, Kondo H, Kano M, Watanabe M, Iino M, Takeshima H. Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity. EMBO J. 26, 1924-1933, 2007.
  8. Kakizawa S, Miyazaki T, Yanagihara D, Iino M, Watanabe M, Kano M. Maintenance of presynaptic function by AMPA receptor-mediated excitatory postsynaptic activity in adult brain. Proc. Natl. Acad. Sci. U. S. A. 102, 19180-19185, 2005.

2. Review Articles

  1. Kakizawa S. Involvement of ROS signal in aging and regulation of brain functions. J Physiol Sci 75, 100003, 2025.
  2. Kakizawa S, Park J, Tonoki A. Biology of cognitive aging across species. Geriatr Gerontol Int 24 (Suppl 1), 15-24, 2023.
  3. Mikami Y, Kakizawa S, Yamazawa T. Essential Roles of Natural Products and Gaseous Mediators on Neuronal Cell Death or Survival. Inter J Mol Sci 17, 1652, 2016.
  4. Kakizawa S. Nitric Oxide-Induced Calcium Release: Activation of Type 1 Ryanodine Receptor, a Calcium Release Channel, through Non-Enzymatic Post-Translational Modification by Nitric Oxide. Frontiers in Endocrinology 4, 142, 2013.
  5. Kakizawa S, Moriguchi S, Ikeda A, Iino M, Takeshima H. Functional crosstalk between cell-surface and intracellular channels mediated by junctophilins essential for neuronal functions. Cerebellum 7, 385-391, 2008.