Requirements for LTP induction by pairing in hippocampal CA1 pyramidal cells.
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 ( approximately 15 s). Surprisingly, we found that this protocol failed to induce LTP, even though large LTP ( approximately 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.
Chen
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HX
Volen Center for Complex Systems, Biology Department, Brandeis University, Waltham, Massachusetts 02454, USA.
Otmakhov
N
N
Lisman
J
J
D000818:Animals; D066298:In Vitro Techniques; D017774:Long-Term Potentiation; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D013569:Synapses / Q000502:physiology; D013746:Tetany