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J Neurophysiol 82: 526-532, 1999;
0022-3077/99 $5.00
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The Journal of Neurophysiology Vol. 82 No. 2 August 1999, pp. 526-532
Copyright ©1999 by the American Physiological Society

Requirements for LTP Induction by Pairing in Hippocampal CA1 Pyramidal Cells

Huan-Xin Chen, Nikolai Otmakhov, and John Lisman

Volen Center for Complex Systems, Biology Department, Brandeis University, Waltham, Massachusetts 02454

Chen, Huan-Xin, Nikolai Otmakhov, and John Lisman. Requirements for LTP Induction by Pairing in Hippocampal CA1 Pyramidal Cells. J. Neurophysiol. 82: 526-532, 1999. The induction of long-term potentiation (LTP) in the hippocampal CA1 region requires both presynaptic activity and large postsynaptic depolarization. A standard protocol for inducing LTP using whole-cell recording is to pair low-frequency synaptic stimulation (100-200 pulses, 1-2 Hz) with a depolarizing voltage-clamp pulse (1-3 min duration). In this standard protocol, a Cs+-based internal solution is used to improve the fidelity of the depolarization produced by voltage-clamp. In an attempt to induce LTP more rapidly, we tried to induce LTP by pairing high-frequency stimulation (200 pulses, 20-100 Hz) with a short depolarization (~15 s). Surprisingly, we found that this protocol failed to induce LTP, even though large LTP (~300% of baseline) could be induced by a subsequent standard protocol in the same cell. Pairing brief high-frequency stimulation at the beginning of a long depolarization (3 min) also did not induce LTP. However, the same high-frequency stimulation at the end of the long depolarization did induce LTP. When similar experiments were done with a K+-based internal solution, pairing high-frequency stimulation with a short depolarization did induce LTP. This indicates that the requirement for long depolarization is related to the use of Cs+. We speculate that, when recording is made with Cs+, a tetanus given at the beginning of depolarization initiates a process that inhibits N-methyl-D-aspartate (NMDA)-dependent LTP. This inhibitory process itself decays away during prolonged depolarization.




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