Maintained LTP and Memory Are Lost by Zn2+Influx into Dentate Granule Cells, but Not Ca2+Influx.
The idea that maintained LTP and memory are lost by either increase in intracellular Zn2+in dentate granule cells or increase in intracellular Ca2+was examined to clarify significance of the increases induced by excess synapse excitation. Both maintained LTP and space memory were impaired by injection of high K+into the dentate gyrus, but rescued by co-injection of CaEDTA, which blocked high K+-induced increase in intracellular Zn2+but not high K+-induced increase in intracellular Ca2+. High K+-induced disturbances of LTP and intracellular Zn2+are rescued by co-injection of 6-cyano-7-nitroquinoxakine-2,3-dione, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist, but not by co-injection of blockers of NMDA receptors, metabotropic glutamate receptors, and voltage-dependent calcium channels. Furthermore, AMPA impaired maintained LTP and the impairment was also rescued by co-injection of CaEDTA, which blocked increase in intracellular Zn2+, but not increase in intracellular Ca2+. NMDA and glucocorticoid, which induced Zn2+release from the internal stores, did not impair maintained LTP. The present study indicates that increase in Zn2+influx into dentate granule cells through AMPA receptors loses maintained LTP and memory. Regulation of Zn2+influx into dentate granule cells is more critical for not only memory acquisition but also memory retention than that of Ca2+influx.
Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan. takedaa@u-shizuoka-ken.ac.jp.
Atsushi
A
Takeda
Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
Haruna
H
Tamano
Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
Marie
M
Hisatsune
Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
Taku
T
Murakami
Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
Hiroyuki
H
Nakada
Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
Hiroaki
H
Fujii
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D059906:Neuroimaging; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D015032:Zinc / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D015032:Zinc; D002118:Calcium
AMPA receptor; Calcium; Dentate granule cell; Memory retention; Zinc