Elsevier

Neuroscience

Volume 102, Issue 1, 2 January 2001, Pages 53-64
Neuroscience

Persistent sodium channel activity mediates subthreshold membrane potential oscillations and low-threshold spikes in rat entorhinal cortex layer V neurons

https://doi.org/10.1016/S0306-4522(00)00455-3Get rights and content

Abstract

Entorhinal cortex layer V occupies a critical position in temporal lobe circuitry since, on the one hand, it serves as the main conduit for the flow of information out of the hippocampal formation back to the neocortex and, on the other, it closes a hippocampal–entorhinal loop by projecting upon the superficial cell layers that give rise to the perforant path. Recent in vitro electrophysiological studies have shown that rat entorhinal cortex layer V cells are endowed with the ability to generate subthreshold oscillations and all-or-none, low-threshold depolarizing potentials. In the present study, by applying current-clamp, voltage-clamp and single-channel recording techniques in rat slices and dissociated neurons, we investigated whether entorhinal cortex layer V cells express a persistent sodium current and sustained sodium channel activity to evaluate the contribution of this activity to the subthreshold behavior of the cells. Sharp-electrode recording in slices demonstrated that layer V cells display tetrodotoxin-sensitive inward rectification in the depolarizing direction, suggesting that a persistent sodium current is present in the cells. Subthreshold oscillations and low-threshold regenerative events were also abolished by tetrodotoxin, suggesting that their generation also requires the activation of such a low-threshold sodium current. The presence of a persistent sodium current was confirmed in whole-cell voltage-clamp experiments, which revealed that its activation “threshold” was negative by about 10 mV to that of the transient sodium current. Furthermore, stationary noise analysis and cell-attached, patch-clamp recordings indicated that whole-cell persistent sodium currents were mediated by persistent sodium channel activity, consisting of relatively high-conductance (∼18 pS) sustained openings.

The presence of a persistent sodium current in entorhinal cortex layer V cells can cause the generation of oscillatory behavior, bursting activity and sustained discharge; this might be implicated in the encoding of memories in which the entorhinal cortex participates but, under pathological situations, may also contribute to epileptogenesis and neurodegeneration.

Section snippets

Slice preparation

The procedures for slice preparation and intracellular recording were followed according to previously published procedures.1 All efforts were made to minimize both the suffering and the number of animals used, and all the experiments were carried out in accordance with the Canadian Council on Animal Care guidelines on the ethical use of animals. In brief, young adult male Long–Evans rats (postnatal days 35–50; Charles River, Quebec, Canada) were decapitated, the brains were removed and a block

Current-clamp analysis of low-threshold, tetrodotoxin-sensitive responses in entorhinal cortex layer V neurons

In a recent study, we have shown that although principal neurons in layer V of the medial EC can be grouped into three distinct morphological categories, the three categories of cells share a number of electrophysiological attributes. The latter include inward rectification in the depolarizing direction and the ability of many of the cells to generate rhythmic, subthreshold membrane potential oscillations and/or slow low-threshold depolarizing potentials that can trigger spike doublets.20

It has

Discussion

The results of the present study demonstrate that the subthreshold intrinsic excitability of EC layer V neurons is largely dominated by a low-threshold sustained sodium current (INaP), which appears to be mainly due to “persistent” sodium channel activity similar to that described previously in EC layer II principal cells.38 Under current-clamp conditions, this voltage-gated “persistent” sodium channel activity causes pronounced inward rectification in the depolarizing direction and is

Acknowledgements

This work has been supported by the Canadian Institutes of Health Research, HFSPO and the North Atlantic Treaty Organization.

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    Permanent address: Dipartimento di Scienze Fisiologiche-Farmacologiche-Cellulari-Molecolari, Sezione di Fisiologia Generale e Biofisica Cellulare, Università degli Studi di Pavia, via Forlanini 6, 27100 Pavia, Italy.

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