NMDA receptors amplify calcium influx into dendritic spines during associative pre- and postsynaptic activation.
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.
Schiller
J
J
Department of Pharmacology, Mayo-Foundation, Rochester, Minnesota 55905, USA.
Schiller
Y
Y
Clapham
D E
DE
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D005971:Glutamates; D018698:Glutamic Acid / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology; D017729:Presynaptic Terminals / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000502:physiology
C102508:(carboxy-2-nitrobenzyl)glutamic acid; D015220:Calcium Channels; D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D002118:Calcium