N-Methyl-d-aspartate (NMDA) receptors have been implicated in epileptogenesis, but how these receptors contribute to epilepsy remains unknown. In particular, their role is likely to be complicated because of their voltage-dependent behavior. Here, the authors investigate how activation of NMDA receptors can affect the intrinsic production of oscillation and the resonance properties of neocortical pyramidal neurons from children with intractable epilepsy. Intracellular whole-cell patch clamp recordings in cortical slices from these patients revealed that pyramidal neurons do not produce spontaneous oscillation under control conditions. However, they did exhibit resonance around 1.5 Hz. On NMDA receptor activation, with bath-applied NMDA (10 μM), the majority of neurons produced voltage-dependent intrinsic oscillation associated with a change in the stability of the neuronal system as reflected by the whole-cell I-V curve. Furthermore, the degree of resonance was amplified while the frequency of resonance was shifted to lower frequencies (∼1 Hz) in NMDA. These results suggest that NMDA receptors may both promote the production of low-frequency oscillation and sharpen the response of the cell to lower frequencies. Both these behaviors may be amplified in tissue from patients with epilepsy, resulting in an increased propensity to generate seizures.
From the *Department of Pediatrics, The University of Chicago, Chicago, Illinois; †Department of Neurological Surgery, Seattle Children';s Research Institute Center for Integrative Brain Research, University of Washington, Seattle, Washington; and ‡Department of Neurosurgery, The University of Chicago, Chicago, Illinois, U.S.A.
The first two authors contributed equally to this work.
Supported by the National Institutes of Health grants T32 GM007281-35 and T32 HD007009-35 (MSTP and GDTP programs at the University of Chicago), the ARCS Foundation, the Falk Foundation, the Epilepsy Foundation, and CINNR & IDDRC (“Tools for Epilepsy Research: Tutorials & Updates” conference, Chicago, IL, August 6-8, 2009).
Address correspondence and reprint requests to Amber Martell, Department of Pediatrics, University of Chicago, 900 E. 57th St., Rm. 4122, Chicago, IL 60637, U.S.A.; e-mail: email@example.com.