---
res:
  bibo_abstract:
  - The time course of Mg(2+) block and unblock of NMDA receptors (NMDARs) determines
    the extent they are activated by depolarization. Here, we directly measure the
    rate of NMDAR channel opening in response to depolarizations at different times
    after brief (1 ms) and sustained (4.6 s) applications of glutamate to nucleated
    patches from neocortical pyramidal neurons. The kinetics of Mg(2+) unblock were
    found to be non-instantaneous and complex, consisting of a prominent fast component
    (time constant approximately 100 micros) and slower components (time constants
    4 and approximately 300 ms), the relative amplitudes of which depended on the
    timing of the depolarizing pulse. Fitting a kinetic model to these data indicated
    that Mg(2+) not only blocks the NMDAR channel, but reduces both the open probability
    and affinity for glutamate, while enhancing desensitization. These effects slow
    the rate of NMDAR channel opening in response to depolarization in a time-dependent
    manner such that the slower components of Mg(2+) unblock are enhanced during depolarizations
    at later times after glutamate application. One physiological consequence of this
    is that brief depolarizations occurring earlier in time after glutamate application
    are better able to open NMDAR channels. This finding has important implications
    for spike-timing-dependent synaptic plasticity (STDP), where the precise (millisecond)
    timing of action potentials relative to synaptic inputs determines the magnitude
    and sign of changes in synaptic strength. Indeed, we find that STDP timing curves
    of NMDAR channel activation elicited by realistic dendritic action potential waveforms
    are narrower than expected assuming instantaneous Mg(2+) unblock, indicating that
    slow Mg(2+) unblock of NMDAR channels makes the STDP timing window more precise.@eng
  bibo_authorlist:
  - foaf_Person:
      foaf_givenName: Bjorn
      foaf_name: Kampa, Bjorn M
      foaf_surname: Kampa
  - foaf_Person:
      foaf_givenName: John
      foaf_name: Clements, John
      foaf_surname: Clements
  - foaf_Person:
      foaf_givenName: Peter M
      foaf_name: Peter Jonas
      foaf_surname: Jonas
      foaf_workInfoHomepage: http://www.librecat.org/personId=353C1B58-F248-11E8-B48F-1D18A9856A87
    orcid: 0000-0001-5001-4804
  - foaf_Person:
      foaf_givenName: Greg
      foaf_name: Stuart, Greg J
      foaf_surname: Stuart
  bibo_doi: '10.1113/jphysiol.2003.058842 '
  bibo_issue: Pt 2
  bibo_volume: 556
  dct_date: 2004^xs_gYear
  dct_publisher: Wiley-Blackwell@
  dct_title: 'Kinetics of Mg(2+) unblock of NMDA receptors: implications for spike-timing
    dependent synaptic plasticity@'
...