NMDA receptors amplify calcium influx into dendritic spines during associative pre- and postsynaptic activation

Nat Neurosci. 1998 Jun;1(2):114-8. doi: 10.1038/363.


Long-term potentiation (LTP) of synaptic strength can be induced by synchronous pre- and postsynaptic activation, and a rise in postsynaptic calcium is essential for induction of LTP. Calcium can enter through both voltage-dependent Ca2+ channels and NMDA-type glutamate receptors, but the relative contributions of these pathways is not known. We have examined this issue in layer V cortical pyramidal neurons, using focal flash photolysis of caged glutamate to mimic synaptic input and two-photon, laser-scanning microscopy to measure calcium levels in dendritic spines. Most of the calcium entry in response to glutamate alone was via voltage-dependent Ca2+ channels, and NMDA receptors accounted for less than 20% of total Ca2+ entry. When glutamate was paired with postsynaptic action potentials, however, the NMDA-receptor-dependent component was selectively amplified. The same is likely to occur during paired physiological pre- and postsynaptic activation, providing a mechanism for the input specificity and Hebbian behavior of LTP.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • Dendrites / metabolism*
  • Glutamates
  • Glutamic Acid / pharmacology
  • Long-Term Potentiation / physiology
  • Presynaptic Terminals / physiology*
  • Pyramidal Cells / physiology
  • Rats
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Synapses / physiology


  • (carboxy-2-nitrobenzyl)glutamic acid
  • Calcium Channels
  • Glutamates
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Calcium