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This Article Full Text Full Text (PDF) All Versions of this Article: 92/4/2346    most recent 00977.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (20) Citing Articles via Google Scholar Google Scholar Articles by Wu, W. W. Articles by Disterhoft, J. F. Search for Related Content PubMed PubMed Citation Articles by Wu, W. W. Articles by Disterhoft, J. F.

Slow Afterhyperpolarization Governs the Development of NMDA Receptor–Dependent Afterdepolarization in CA1 Pyramidal Neurons During Synaptic Stimulation

Department of Physiology and Institute for Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611

Submitted 9 October 2003; accepted in final form 6 June 2004

CA1 pyramidal neurons from animals that have acquired a hippocampus-dependent task show a reduced slow postburst afterhyperpolarization (sAHP). To understand the functional significance of this change, we examined and characterized the sAHP activated by different patterns of synaptic stimuli and its impact on postsynaptic signal integration. Whole cell current-clamp recordings were performed on rat CA1 pyramidal neurons, and trains of stratum radiatum stimuli varying in duration, frequency, and intensity were used to activate the AHP. At –68 mV, a short train of subthreshold stimuli (20–150 Hz) generated only the medium AHP. In contrast, just two suprathreshold stimuli >50 Hz triggered a prominent sAHP sensitive to bath-applications of isoproterenol, carbachol, or intracellularly applied BAPTA, suggesting that the underlying current is the Ca²⁺-activated K⁺ current, the sI_AHP. The sAHP magnitude was positively related to stimulus train duration and frequency, consistent with its dependence on intracellular Ca²⁺ accumulation for activation. About 20% of neurons recorded did not have a sAHP. In response to high-frequency suprathreshold stimuli, these neurons developed a pronounced afterdepolarization (ADP) and multiple action potential firing. The ADP magnitude increased with successive stimuli and was positively related to stimulus intensity and frequency. It was sensitive to bath-applications of thapsigargin and nitrendipine, and abolished by D-AP5, indicating that it is supported by intracellular Ca²⁺ release, the L-type Ca²⁺ influx, and N-methyl-D-aspartate (NMDA) receptor–mediated influx. In the presence of D-AP5, we were unable to trigger an ADP with maximal stimulus intensity. Pharmacologically eliminating the sAHP allowed neurons to develop an ADP with the original stimulus train. We propose that the slow AHP acts to facilitate Mg²⁺ re-block of the activated NMDA receptors, thereby reducing temporal summation and preventing an NMDA receptor–dependent ADP during intense synaptic events. Neuromodulation of the sAHP may thus affect information throughput and regulate NMDA receptor–mediated plasticity.

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