Induction of synaptic depression by high-frequency stimulation in area CA1 of the rat hippocampus: Modeling and experimental studies
Introduction
It is reported that stimulation frequency lower than 10 Hz induced long-term depression (LTD), while that higher than this induced long-term potentiation (LTP) [4], [8], [9]. When the stimulation frequency is increased beyond 100 Hz, however, it is not clear whether the magnitude of LTP is kept constant, increased or even decreased. It was reported that the increased number of θ-burst stimulation reduced the magnitude of LTP [7]. This suggests that the stronger stimulation, which will lead to the very large increase in intracellular calcium concentration ([Ca2+]i) of postsynaptic cells, reduced the magnitude of LTP. What will be the results if the stimulation is much stronger? To see this, we performed both modeling and experimental studies and found the induction of LTD instead of LTP by high-frequency stimulation of 300 Hz (HFS-LTD).
Section snippets
Materials and methods
Hippocampal slices were prepared from Sprague–Dawley rats (21–25 days old). Rats were anesthetized with ether and decapitated. Hippocampi were dissected rapidly and transverse slices (500 μm thick) were cut using a rotary tissue slicer at room temperature, then maintained in an incubation chamber in the presence of gassed (95% O2–5% CO2) extracellular solution containing (in mM): 124 NaCl, 3.0 KCl, 2.0 CaCl2, 2.0 MgSO4, 1.25 NaHCO3 and 10 glucose for at least 2 h at 30 °C. Immediately before each
Results
Simulations were performed at stimulation frequencies from 1 to 500 Hz, and DC was plotted as a function of frequency or [Ca2+]i (Fig. 2A top and middle panels). DC was negative and positive at frequencies lower than 12 Hz and between 12 and 200 Hz, respectively. At frequency higher than 200 Hz, however, DC was negative again, suggesting the induction of high-frequency stimulation-induced LTD (HFS-LTD, Fig. 2A top panel). Thin and thick arrows indicate zero-crossing position from negative to
Discussion
In the present study, 300 Hz-1s was used as a HFS-LTD inducing stimulus. Such high-frequency stimuli may cause unexpected firing. However, it is probable that larger [Ca2+]i increase will be seen at this frequency, and this will lead to the induction of HFS-LTD as suggested by the middle panel of Fig. 2A. The important implication of the present study is that at high [Ca2+]i the synaptic efficacy may possibly be depressed.
The Mg2+ concentration in the bathing medium was 1 mM in the present
Kazuhisa Ichikawa is a Professor of Department of Brain and Bioinformation Science at Kanazawa Institute of Technology. He received his Ph.D. in Biophysics from Kyoto University in 1989. He is working as a theoretical neuroscientists. He is in charge of modeling and simulation, and the analysis of the results. His long range research goal is to elucidate the mechanism of learning and memory in a computer executable expression.
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Kazuhisa Ichikawa is a Professor of Department of Brain and Bioinformation Science at Kanazawa Institute of Technology. He received his Ph.D. in Biophysics from Kyoto University in 1989. He is working as a theoretical neuroscientists. He is in charge of modeling and simulation, and the analysis of the results. His long range research goal is to elucidate the mechanism of learning and memory in a computer executable expression.
Akemi Hoshino is a Postdoctoral Fellow of Department of Pathology at New York University School of Medicine. She received her Ph.D. (Medical Science) from Graduate School of Medicine in Yamagata University in 2005. She is in charge of obtaining experimental data in this paper.
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