PMID- 18057106
OWN - NLM
STAT- MEDLINE
DCOM- 20080612
LR  - 20141120
IS  - 0022-3077 (Print)
IS  - 0022-3077 (Linking)
VI  - 99
IP  - 2
DP  - 2008 Feb
TI  - Recruiting extrasynaptic NMDA receptors augments synaptic signaling.
PG  - 524-33
AB  - N-Methyl-d-aspartate receptor (NMDAR) activation may promote cell survival or 
      initiate cell death, with the outcome dependent on whether synaptic or 
      extrasynaptic receptors are activated. Similarly, this differential activation 
      has been proposed to govern the direction of plasticity. However, the 
      physiological parameters necessary to activate extrasynaptic NMDARs in brain 
      slices remain unknown. Using the irreversible use-dependent NMDAR antagonist 
      MK-801 to isolate extrasynaptic NMDARs, we have tested the ability of 
      short-stimulation trains from 5 to 400 Hz to activate these receptors on CA1 
      hippocampal slice pyramidal neurons. Frequencies as low as 25 Hz engage 
      extrasynaptic NMDARs, with maximal activation at frequencies between 100 and 200 
      Hz. Since similar bursts of synaptic input occur during exploratory behavior in 
      rats, our results demonstrate that "extrasynaptic" NMDARs regularly participate 
      in synaptic transmission. Further, 175-Hz-stimulation trains activate all 
      available synaptic and extrasynaptic dendritic NMDARs, suggesting these NMDARs 
      act as synaptic receptors as needed, transiently increasing synaptic strength. 
      Thus extrasynaptic NMDARs play a vital role in synaptic physiology, calling into 
      question their status as "extrasynaptic."
FAU - Harris, Alexander Z
AU  - Harris AZ
AD  - Dominick P. Purpura Department of Neuroscience, Albert Einstein College of 
      Medicine, Bronx, NY 10461, USA.
FAU - Pettit, Diana L
AU  - Pettit DL
LA  - eng
GR  - K22 ES-00359/ES/NIEHS NIH HHS/United States
GR  - R21 NS-051536/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20071205
PL  - United States
TA  - J Neurophysiol
JT  - Journal of neurophysiology
JID - 0375404
RN  - 0 (Anesthetics, Local)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Oregon Green BAPTA-dextran)
RN  - 0 (Organic Chemicals)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 4368-28-9 (Tetrodotoxin)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 76326-31-3 (2-amino-5-phosphopentanoic acid)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Anesthetics, Local/pharmacology
MH  - Animals
MH  - Animals, Newborn
MH  - Dendrites/drug effects/radiation effects
MH  - Dizocilpine Maleate/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Dose-Response Relationship, Radiation
MH  - Electric Stimulation/methods
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Excitatory Postsynaptic Potentials/drug effects/physiology/radiation effects
MH  - Hippocampus/cytology
MH  - In Vitro Techniques
MH  - Neurons/cytology/drug effects/*physiology/radiation effects
MH  - Organic Chemicals/metabolism
MH  - Patch-Clamp Techniques
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/*physiology
MH  - Synaptic Transmission/drug effects/*physiology/radiation effects
MH  - Tetrodotoxin/pharmacology
MH  - Valine/analogs & derivatives/pharmacology
EDAT- 2007/12/07 09:00
MHDA- 2008/06/13 09:00
CRDT- 2007/12/07 09:00
PHST- 2007/12/07 09:00 [pubmed]
PHST- 2008/06/13 09:00 [medline]
PHST- 2007/12/07 09:00 [entrez]
AID - 01169.2007 [pii]
AID - 10.1152/jn.01169.2007 [doi]
PST - ppublish
SO  - J Neurophysiol. 2008 Feb;99(2):524-33. doi: 10.1152/jn.01169.2007. Epub 2007 Dec 
      5.