Long-term potentiation during whole-cell recording in rat hippocampal slices.
Factors involved in the production of long-term potentiation in the CA1 region of rat hippocampal slices were examined using whole-cell voltage clamp recordings. The pairing of postsynaptic membrane depolarization with tetanic stimulation produced a reliable long-lasting enhancement of synaptic currents provided that the pairing was performed within 15 min after establishing intracellular contact. This time could be extended to 30 min by including adenosine triphosphate and guanosine triphosphate in the recording pipette. Once established, the potentiation persisted for 3 h or more. The washout of long-term potentiation generating ability was not correlated with a rundown in baseline synaptic currents or in the N-methyl-D-aspartate receptor-mediated component of synaptic responses, but followed a time course similar to the loss of calcium spikes. Long-term potentiation could be reliably produced by depolarizing the postsynaptic membrane to -40 or -20 mV during the tetanus, but decreased when the membrane was held at membrane potentials greater than 0 mV. At -20 mV, 50 microM 2-amino-5-phosphonovalerate blocked the potentiation but this agent was ineffective at +40 mV. In contrast, 50 microM verapamil, a calcium channel blocker, failed to alter long-term potentiation at -20 mV but blocked the enhancement at +40 mV. These results suggest that whole-cell recording causes a washout of postsynaptic factors important in the initiation of long-term potentiation. However, these factors are less important in maintaining the potentiation. Furthermore, depending on the postsynaptic membrane potential during tetanic stimulation, voltage-gated calcium channels contribute to CA1 long-term potentiation.
Kato
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Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110.
Clifford
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DB
Zorumski
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CF
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D004558:Electric Stimulation; D005110:Extracellular Space / Q000502:physiology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011712:Pyramidal Tracts / Q000166:cytology; D051381:Rats; D013569:Synapses / Q000187:drug effects; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D015220:Calcium Channels; D002614:Chelating Agents; D015763:2-Amino-5-phosphonovalerate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D014700:Verapamil; D002118:Calcium