Get access

The role of voltage dependence of the NMDA receptor in cellular and network oscillation

Authors

  • Amber L. Martell,

    1. Departments of Pediatrics and Neurology, The University of Chicago, KCBD 4124, 900 E 57th Street, Chicago, IL 60637, USA
    Search for more papers by this author
  • Jan-Marino Ramirez,

    1. Departments of Pediatrics and Neurology, The University of Chicago, KCBD 4124, 900 E 57th Street, Chicago, IL 60637, USA
    Search for more papers by this author
  • Robert E. Lasky,

    1. Departments of Pediatrics and Neurology, The University of Chicago, KCBD 4124, 900 E 57th Street, Chicago, IL 60637, USA
    Search for more papers by this author
  • Jennifer E. Dwyer,

    1. Departments of Pediatrics and Neurology, The University of Chicago, KCBD 4124, 900 E 57th Street, Chicago, IL 60637, USA
    Search for more papers by this author
  • Michael Kohrman,

    1. Departments of Pediatrics and Neurology, The University of Chicago, KCBD 4124, 900 E 57th Street, Chicago, IL 60637, USA
    Search for more papers by this author
  • Wim van Drongelen

    1. Departments of Pediatrics and Neurology, The University of Chicago, KCBD 4124, 900 E 57th Street, Chicago, IL 60637, USA
    2. Computation Institute, Committee on Computational Neuroscience, The University of Chicago, Chicago, IL, USA
    Search for more papers by this author

  • Computer code is available: please contact the corresponding author for a copy of the Matlab scripts used in this text.

W. van Drongelen, 1The University of Chicago, as above.
E-mail: wvandron@peds.bsd.uchicago.edu

Abstract

Unraveling the mechanisms underlying oscillatory behavior is critical for understanding normal and pathological brain processes. Here we used electrophysiology in mouse neocortical slices and principles of nonlinear dynamics to demonstrate how an increase in the N-methyl-d-aspartic acid receptor (NMDAR) conductance can create a nonlinear whole-cell current–voltage (I–V) relationship which leads to changes in cellular stability. We discovered two behaviorally and morphologically distinct pyramidal cell populations. Under control conditions, both cell types responded to depolarizing current injection with regular spiking patterns. However, upon NMDAR activation, an intrinsic oscillatory (IO) cell type (= 44) showed a nonlinear whole-cell I–V relationship, intrinsic voltage-dependent oscillations plus amplification of alternating input current, and these properties persisted after disabling action potential generation with tetrodotoxin (TTX). The other non-oscillatory (NO) neuronal population (= 24) demonstrated none of these behaviors. Simultaneous intra- and extracellular recordings demonstrated the NMDAR’s capacity to promote low-frequency seizure-like network oscillations via its effects on intrinsic neuronal properties. The two pyramidal cell types demonstrated different relationships with network oscillation – the IO cells were leaders that were activated early in the population activity cycle while the activation of the NO cell type was distributed across network bursts. The properties of IO neurons disappeared in a low-magnesium environment where the voltage dependence of the receptor is abolished; concurrently, the cellular contribution to network oscillation switched to synchronous firing. Thus, depending upon the efficacy of NMDAR in altering the linearity of the whole-cell I–V relationship, the two cell populations played different roles in sustaining network oscillation.

Get access to the full text of this article

Ancillary