The Journal of Neurophysiology Vol. 77 No. 2 February 1997, pp. 812-825
Copyright ©1997 The American Physiological Society

Induction of LTD in the Dentate Gyrus In Vitro Is NMDA Receptor Independent, but Dependent on Ca²⁺ Influx via Low-Voltage-Activated Ca²⁺ Channels and Release of Ca²⁺ From Intracellular Stores

Yue Wang, Michael J. Rowan, and Roger Anwyl

Departments of Physiology and Pharmacology and Therapeutics, Trinity College, Dublin 2, Ireland

Wang, Yue, Michael J. Rowan, and Roger Anwyl. Induction of LTD in the dentate gyrus in vitro is NMDA receptor independent, but dependent on Ca²⁺ influx via low-voltage-activated Ca²⁺ channels and release of Ca²⁺ from intracellular stores. J. Neurophysiol. 77: 812-825, 1997. The mechanisms of the induction of long-term depression (LTD) of field excitatory postsynaptic potentials (EPSPs) and whole cell patch-clamped excitatory postsynaptic currents (EPSCs) were studied in the dentate gyrus of the rat hippocampus. LTD of field EPSPs measuring 40% of control at 30 min poststimulation was induced by low-frequency stimulation consisting of 900 pulses at 1 Hz. LTD of EPSCs measuring 37% of control was induced by a pairing procedure consisting of 60 pulses at 1 Hz applied under voltage clamp at a holding potential of 40 mV. The induction of LTD of field EPSPs was dependent on an influx of extracellular calcium, being reduced in a low-Ca²⁺ (0.8 mM) medium. However, substantial LTD (26%) was still induced in such a medium, demonstrating the relatively low sensitivity of LTD induction to the level of extracellular Ca²⁺. A high concentration of the N-methyl-D-aspartate receptor antagonist D()-2-amino-5-phosphonopentanoic acid (D-AP5) (100 µM) did not significantly inhibit the induction of LTD of EPSCs evoked by the intracellular pairing procedure. D-AP5 partially reduced the magnitude of LTD of field EPSPs, but substantial LTD was still induced in the presence of AP5. The induction of LTD was strongly inhibited by Ni²⁺ (50 µM) but not by nifedipine (10 µM), indicating that Ca²⁺ influx via T-type, but not L-type, Ca²⁺ channels is required for the induction of LTD. The induction of LTD was strongly inhibited by thapsigargin, an agent known to deplete intracellular Ca²⁺ stores. The induction of LTD, but not long-term potentiation (LTP), was also strongly inhibited by ruthenium red, an agent known to block the ryanodine receptors located on intracellular Ca²⁺ stores. These results demonstrate that Ca²⁺ release from intracellular Ca²⁺ stores is required for the induction of LTD, but not LTP. The results of the present experiments suggest that the induction of LTD involves the entry of Ca²⁺ via low-voltage-activated voltage-gated Ca²⁺ channels followed by release of Ca²⁺ from intracellular ryanodine-receptor-sensitive Ca²⁺ stores.

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