Mechanisms involved in age-related memory impairment and sleep in Drosophila

2013 Fiscal Year Final Research Report

• Project/Area Number: 23500394
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: Tokyo Metropolitan Institute of Medical Science (2013); Tokyo Metropolitan University (2011-2012)
• Principal Investigator: HORIUCHI Junjiro 公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 主席研究員 (80392364)
• Project Period (FY): 2011 – 2013
• Keywords: 学習 / 記憶 / 加齢性記憶障害 / 睡眠

Research Abstract

As we age, we suffer a decrease in memory. This phenomenon is known as age-related memory impairment (AMI). AMI is a serious social and medical problem, and it becomes more severe as we age. To understand the causes of AMI, we studied it in Drosophila. We found that aging causes an increase in a protein, pyruvate carboxylase (PC). PC is found in glia, cells that interact with neurons. Increasing PC activity in glia inhibits production D-serine, a neuromodulator that regulates neuronal activity. Feeding D-serine to old flies decreases AMI. This indicates that decreased glial production of the neuromodulator D-serine is a cause of AMI.
In a second project, we studied sleep in Drosophila. Sleep is essential for many organisms, but its regulation is still unclear. We found that sleep is regulated by the Ca2+/calmodulin signaling pathway, a pathway known to control many biological processes. Our results suggest a mechanism through which sleep may be linked to other biological processes.

Research Products

• [Journal Article] Fasting launches CRTC to facilitate long-term memory formation in Drosophila (2013)
  • Author(s): Hirano, Y., Masuda, T., Naganos, S., Matsuno, M., Ueno, K., Miyashita, T., Horiuchi, J., Saitoe, M
  • Journal Title: Science Volume: 339(6118) Pages: 443-6
  • Peer Reviewed
• [Journal Article] Long-term enhancement of synaptic transmission between antennal lobe and mushroom body in cultured Drosophila brain (2013)
  • Author(s): Ueno, K., Naganos, S., Hirano, Y., Horiuchi, J., Saitoe, M
  • Journal Title: J Physiol Volume: 591(Pt1) Pages: 287-302
  • Peer Reviewed
• [Journal Article] Mg^<2+> block of Drosophila NMDA receptors is required for long-term memory formation and CREB-dependent gene expression (2012)
  • Author(s): Miyashita, T., Oda, Y., Horiuchi, J., Yin, J. C-P., Morimoto, T., Saitoe, M
  • Journal Title: Neuron Volume: 74(5) Pages: 887-98
  • Peer Reviewed
• [Journal Article] Mutations in the Drosophila insulin receptor substrate, CHICO, impair olfactory associative learning (2012)
  • Author(s): Naganos, S., Horiuchi, J., Saitoe, M
  • Journal Title: Neurosci Res Volume: 73(1) Pages: 49-55
  • Peer Reviewed
• [Journal Article] Reactive oxygen species are not involved in the onset of age-related memory impairment in Drosophila (2012)
  • Author(s): Hirano, Y., Kuriyama, Y., Miyashita, T., Horiuchi, J., Saitoe, M
  • Journal Title: Genes Brain Behav Volume: 11(1) Pages: 79-86
  • Peer Reviewed
• [Journal Article] Calcineurin and its regulator Sra/DSCR1 are essential for sleep in Drosophila (2011)
  • Author(s): Nakai, Y., Horiuchi, J., Tsuda, M., Takeo, S., Akahori, S., Matsuo, T., Kume, K., Aigaki, T
  • Journal Title: J Neurosci Volume: 31(36) Pages: 12759-12766
  • Peer Reviewed
• [Presentation] Age-related memory impairment in Drosophila is caused by an oxidative stress-independent impairment of glial neuromodulator release (2014)
  • Author(s): Horiuchi, J., Yamazaki, Y., Saitoe, M
  • Organizer: 2013 Neurobiology of Drosophila meeting at Cold Spring Harbor Laboratory
  • Place of Presentation: Cold Spring Harbor, NY, USA
  • Year and Date: 2014-10-04
• [Presentation] Olfactory aversive conditioning forms two distinct memory components in Drosophila (2014)
  • Author(s): Naganos, S., Ueno, K., Horiuchi, J., Saitoe, M
  • Organizer: 2013 Neurobiology of Drosophila meeting at Cold Spring Harbor Laboratory
  • Place of Presentation: Cold Spring Harbor, NY, USA
  • Year and Date: 2014-10-03
• [Presentation] Neuron-glial communication induces glial protein synthesis required for formation of long-term memories (2013)
  • Author(s): Matsuno, M., Horiuchi, J., Saitoe, M
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2013-12-04
• [Presentation] Long-term memory formation requires neuron-glia signaling to induce protein synthesis (2013)
  • Author(s): Matsuno, M., Horiuchi, J., Saitoe, M
  • Organizer: CSFN2013 Cell Symposia - The Networked Brain
  • Place of Presentation: San Diego, USA
  • Year and Date: 2013-11-08
• [Presentation] Coincident stimulation of two independent pathways triggers dopamine release which enhances synaptic transmission in Drosophila mushroom bodies (2013)
  • Author(s): 上野耕平, 堀内純二郎, 齊藤実
  • Organizer: 第11回世界生物学的精神医学会国際会議
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2013-06-22
• [Presentation] Improving memory in Drosophila (2011)
  • Author(s): Horiuchi, J
  • Organizer: 2011 Senryaku Kenkyu Center Symposium
  • Place of Presentation: Tokyo Metropolitan University, Tokyo, Japan
  • Year and Date: 2011-11-22
• [Presentation] Regulation of sleep in Drosophila by components of the Ca^<2+>/calmodulin signaling pathway (2011)
  • Author(s): Horiuchi, J., Nakai, Y., Akahori, S., Aigaki, T
  • Organizer: 2011 Neurobiology of Drosophila meeting
  • Place of Presentation: Cold Spring Harbor, NY, USA
  • Year and Date: 2011-10-05