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The Journal of Neuroscience, March 15, 1999, 19(6):1976-1987
Mechanisms of Calcium Influx into Hippocampal Spines:
Heterogeneity among Spines, Coincidence Detection by NMDA Receptors,
and Optical Quantal Analysis
Rafael
Yuste1,
Ania
Majewska1,
Sydney S.
Cash1, and
Winfried
Denk2
1 Department of Biological Sciences, Columbia
University, New York, New York 10027, and 2 Biological
Computation Research Department, Bell Laboratories Lucent Technologies,
Murray Hill, New Jersey 07974
Dendritic spines receive most excitatory inputs in the vertebrate
brain, but their function is still poorly understood. Using two-photon
calcium imaging of CA1 pyramidal neurons in rat hippocampal slices, we
investigated the mechanisms by which calcium enters into individual
spines in the stratum radiatum. We find three different pathways for
calcium influx: high-threshold voltage-sensitive calcium channels, NMDA
receptors, and an APV-resistant influx consistent with
calcium-permeable AMPA or kainate receptors. These pathways vary among
different populations of spines and are engaged under different
stimulation conditions, with peak calcium concentrations reaching >10
µM. Furthermore, as a result of the biophysical
properties of the NMDA receptor, the calcium dynamics of spines are
exquisitely sensitive to the temporal coincidence of the input and
output of the neuron. Our results confirm that individual spines are chemical compartments that can perform coincidence detection. Finally,
we demonstrate that functional studies and optical quantal analysis of
single, identified synapses is feasible in mammalian CNS neurons in
brain slices.
Key words:
dendrites; spines; quantal; calcium; NMDA; hippocampus; two-photon microscopy
Copyright © 1999 Society for Neuroscience 0270-6474/99/1961976-12$05.00/0
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