RT Journal Article
SR Electronic
T1 Pattern-Dependent Role of NMDA Receptors in Action Potential Generation: Consequences on Extracellular Signal-Regulated Kinase Activation
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7032
OP 7039
DO 10.1523/JNEUROSCI.1579-05.2005
VO 25
IS 30
A1 Meilan Zhao
A1 J. Paige Adams
A1 Serena M. Dudek
YR 2005
UL http://www.jneurosci.org/content/25/30/7032.abstract
AB Synaptic long-term potentiation is maintained through gene transcription, but how the nucleus is recruited remains controversial. Activation of extracellular signal-regulated kinases (ERKs) 1 and 2 with synaptic stimulation has been shown to require NMDA receptors (NMDARs), yet stimulation intensities sufficient to recruit action potentials (APs) also appear to be required. This has led us to ask the question of whether NMDARs are necessary for AP generation as they relate to ERK activation. To test this, we examined the effects of NMDAR blockade on APs induced with synaptic stimulation using whole-cell current-clamp recordings from CA1 pyramidal cells in hippocampal slices. NMDAR antagonists were found to potently inhibit APs generated with 5 and 100 Hz synaptic stimulation. Blockade of APs and ERK activation could be overcome with the addition of the GABAA antagonist bicuculline, indicating that APs are sufficient to activate signals such as ERK in the nucleus and throughout the neuron in the continued presence of NMDAR antagonists. Interestingly, no effects of the NMDAR antagonists were observed when theta-burst stimulation (TBS) was used. This resistance to the antagonists is conferred by temporal summation during the bursts. These results clarify findings from a previous study showing that ERK activation induced with TBS is resistant to 2-amino-5-phosphonovalerate, in contrast to that induced with 5 or 100 Hz stimulation, which is sensitive. By showing that NMDAR blockade inhibits AP generation, we demonstrate that a major role that NMDARs play in cell-wide and nuclear ERK activation is through their contribution to action potential generation.