Human SCINT Seminar (10) - 1
Event Date: 2005-09-21 15:30
| Date: 2005.9.21 (Wed) 15:30-17:45
Place: General Research Building, Room 630
Time: 15:30-16:30
Speaker: Shigetoshi Kawahara
Title: Classical eyeblink conditioning and its application to the age-related deseases in the brain.
Keywords: mice, classical conditioning, aging, cerebellum, hippocampus
Affiliation: Graduate School of Pharmaceutical Sciences
Position: Associate Professor
Laboratory: Laboratory of Neurobiophysics
Disciplines: Behavioral Neuroscience
Societies and Conferences: Japan Neuroscience Society, Pharmaceutical Society of Japan, Biophysical Society of Japan, Society for Neuroscience
Bibliography: Shigetoshi Kawahara, Classical eyeblink conditioning and its application to the age-related deseases in the brain., Human Science Integration Seminar Abstracts, No. 10, pp. 1, 2005.
(Please use this bibliography when you cite this abstract.)
Abstract:
In classical conditioning of the eyeblink response, the temporal relationship between the conditioned stimulus (tone) and unconditioned stimulus (eye-shock) determines the critical brain areas for this learning: the cerebellum and the brainstem are essential in delay paradigm, and the hippocampus is also required in trace paradigm. In addition, there are many parallels among mammalian species, including human beings. Therefore, this learning task is a powerful tool for studying brain aging.
Using this learning task, we found that the senescence-accelerated mouse SAMP8 showed a severe impairment in both delay and trace paradigms even at 2 months of age. These results suggest that the essential neural circuitry is severely impaired in SAMP8.
We also examined 2-, 6-, 12, and 18-month-old C57BL6/J mice and found that 12- and 18-month-old mice exhibited severe impairment in delay paradigm, while they showed a mild impairment in trace paradigm. These results suggest that critical age-related deficits occur between 6 and 12 months old. To investigate a possible involvement of the hippocampus to this age-related impairment, we performed bilateral hippocampal ablation before delay conditioning. Hippocampus-lesioned 12-month-old mice showed a moderate restoration of learning ability, suggesting a contribution of the hippocampus to the age-related impairment in delay eyeblink conditioning.
References:
1. Kotani S, Kawahara S, Kirino Y, “Purkinje cell activity during classical eyeblink conditioning in decerebrate guinea pigs,” Brain Res., in press.
2. Takehara-Nishiuchi K, Kawahara S, Kirino Y, “NMDA receptor-dependent processes in the medial prefrontal cortex are important for acquisition and the early stage of consolidation during trace but not delay eyeblink conditioning,” Learn. Mem., 12, 606-614 (2005).
3. Takatsuki K, Kawahara S, Mishina M, Kirino Y, “Characterization of hippocampal theta rhythm in wild-type mice and glutamate receptor subunit delta2 mutant mice during eyeblink conditioning with a short trace interval,” Brain Res., 1063,159-167 (2005).
4. Kato Y, Takatsuki K, Kawahara S, Fukunaga S, Mori H, Mishina M, Kirino Y, “NMDA receptors play important roles in acquisition and expression of the eyeblink conditioned response in glutamate receptor subunit delta2 mutant mice,” Neurosci., 135, 1017-1023 (2005).
5. Toshiro Sakamoto, Kanako Takatsuki, Shigenori Kawahara, Yutaka Kirino, Hiroaki Niki, and Masayoshi Mishina1 “Role of hippocampal NMDA receptors in trace eyeblink conditioning,” Brain Res. 1039, 130–136 (2005).
6. Takehara K, Kawahara S, Munemoto Y, Kuriyama H, Mori H, Mishina M, Kirino Y, “The NMDA receptor GluRepsilon2 is important for delay and trace eyeblink conditioning in mice,” Neurosci. Lett., 364, 43-47 (2004).
7. Kotani S, Kawahara S, Kirino Y, “Purkinje cell activity during learning a new timing in classical eyeblink conditioning,” Brain Res. 994, 193-202 (2003)
8. Takehara K, Kawahara S, Kirino Y, “Time-dependent reorganization of the brain components underlying memory retention in trace eyeblink conditioning,” J. Neurosci. 23, 9897–9905 (2003).
9. Kotani S, Kawahara S, Kirino Y “Trace eyeblink conditioning in decerebrate guinea pigs,” Eur. J. Neurosci., 17, 1445-1454 (2003).
10. Takatsuki K, Kawahara S, Kotani S, Fukunaga S, Mori H, Mishina M, Kirino Y, “The hippocampus plays an important role in eyeblink conditioning with a short trace interval in glutamate receptor subunit delta2 mutant mice,” J. Neurosci., 23, 17–22 (2003).
11. Kishimoto Y, Fujimichi R, Araishi K, Kawahara S, Kano M, Aiba A, Kirino Y , “mGluR1 in cerebellar Purkinje cells is required for normal association of temporally contiguous stimuli in classical conditioning,” Eur. J. Neurosci., 16, 2416-2424 (2002).
12. Takehara K, Kawahara S, Takatsuki K, Kirino Y, “Time-limited role of the hippocampus in the memory for trace eyeblink conditioning in mice,” Brain Res., 951, 183-190 (2002).
13. Kotani S, Kawahara S, Kirino Y, “Classical eyeblink conditioning in decerebrate guinea pigs,” Eur. J. Neurosci., 15, 1267-1270 (2002).
14. Kanako Takatsuki, Shigenori Kawahara, Sadaharu Kotani, Hisashi Mori, Masayoshi Mishina, and Yutaka Kirino (2002) Hippocampal damage disrupts eyeblink conditioning in mice lacking glutamate receptor subunit delta2,” Journal of Biological Physics 28, 539-547.
15. Kanako Takatsuki, Shigenori Kawahara, Hisashi. Mori, Masayoshi Mishina and Yutaka Kirino, “Scopolamine impairs eyeblink conditioning in the cerebellar LTD-deficient mice,” NeuroReport, 13, 159-162 (2002)
16. Yasushi Kishimoto, Shigenori Kawahara, Ryoko Fujimichi, Hisashi Mori, Masayoshi Mishina and Yutaka Kirino, “Impairment of eyeblink conditioning in GluRdelta2-mutant mice depends on the temporal overlap between conditioned and unconditioned stimuli,” Eur. J. Neurosci,. 14, 1515-1521 (2001).
17. Kishimoto Y, Suzuki M, Kawahara S, Kirino Y (2001) Age-dependent impairment of delay and trace eyeblink conditioning in mice. Neuroreport 12, 3349-3352.
18. Kishimoto Y, Hirono M, Sugiyama T, Kawahara S, Nakao K, Kishio M, Katsuki M, Yoshioka T, Kirino Y (2001) Impaired delay but normal trace eyeblink conditioning in PLCbeta4 mutant mice. Neuroreport 12, 2919-2922.
19. Takatsuki K, Kawahara S, Takehara K, Kishimoto Y, Kirino Y (2001) Effects of noncompetitive NMDA channel blocker MK-801 on classical eyeblink conditioning in mice. Neuropharmcol 41, 618-628.
20. Kishimoto Y, Kawahara S, Mori H, Mishina M, Kirino Y (2001) Long-trace interval eyeblink conditioning is impaired in mutant mice lacking NMDA receptor subunit epsilon1. Eur J Neurosci 13: 1221-1227.
21. Kishimoto Y, Kawahara S, Suzuki M, Mori H, Mishina M, Kirino Y (2001) Classical eyeblink conditioning in glutamate receptor subunit delta2 mutant mice is impaired in delay paradigm but not in trace paradigm. Eur J Neurosci 13: 1249-1253.
22. Kishimoto Y, Kawahara S, Kirino Y, Kadotani H, Nakamura Y, Ikeda M, Yoshioka T (1997) Conditioned eyeblink response is impaired in mutant mice lacking NMDA receptor subunit NR2A. Neuroreport 8: 3717-3721.
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