N-methyl-D-aspartate receptors (NMDARs) govern synaptic plasticity, development, and neuronal response to insult. Prolonged activation of NMDARs such as during an insult may activate secondary currents or modulate Mg2+ sensitivity, but the conditions under which these occur are not fully defined. We re-examined the effect of prolonged NMDAR activation in juvenile mouse hippocampal slices. NMDA (10 µM) elicited current with the expected negative-slope conductance in the presence of 1.2 mM Mg2+. However, several minutes of continued NMDA exposure elicited additional inward current at -70 mV. Higher concentrations of NMDA (100 µM) elicited the current more rapidly. The additional current was not dependent on Ca2+, network activity, or metabotropic NMDAR function and did not persist upon agonist removal. Voltage ramps revealed no alteration of either reversal potential or NMDA-elicited conductance between -30 mV and +50 mV. The result was a more linear NMDA current-voltage relationship. The current linearization was also induced in interneurons and in mature dentate granule neurons but not immature dentate granule cells, dissociated cultured hippocampal neurons, or nucleated patches excised from CA1 pyramidal neurons. Comparative simulations of NMDA application to a CA1 pyramidal neuron and to a cultured neuron revealed that linearization can be explained by space clamp errors arising from gradual recruitment of distal dendritic NMDARs. We conclude that persistent secondary currents do not strongly contribute to NMDAR responses in juvenile mouse hippocampus, and careful discernment is needed to exclude contributions of clamp artifacts to apparent secondary currents.
- space clamp
- dentate granule neuron
- Copyright © 2017, Journal of Neurophysiology