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This Article Full Text Full Text (PDF) Supplemental data All Versions of this Article: 582/2/583    most recent jphysiol.2007.130286v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Awatramani, G. B. Articles by Murphy, T. H. Search for Related Content PubMed PubMed Citation Articles by Awatramani, G. B. Articles by Murphy, T. H. Related Collections Neuroscience

¹ University of British Columbia, 2255 Wesbrook Mall, Vancouver, British Columbia, Canada V6T 1Z3
² Department of Biology, Box 3020 Stn CSC, University of Victoria, Victoria, British Columbia, Canada V8W 3N5

To understand how information is coded at single hippocampal synapses during high-frequency activity, we imaged NMDA receptor-mediated Ca²⁺ responses in spines of CA1 neurons using two-photon microscopy. Although discrete quantal events were not readily apparent during continuous theta-burst stimulation (TBS), we found that the steady-state dendritic Ca²⁺ response was spatially restricted (half-width < 1 µm), voltage dependent and sensitive to MK-801, indicating that that it was mediated by activation of NMDA receptors at single synapses. Partial antagonism of NMDA receptors caused a similar reduction of NMDA EPSCs (measured at the soma) and local dendritic Ca²⁺ signals, suggesting that, like EPSCs, the steady-state Ca²⁺ signal was made up of a linear addition of quantal events. Statistical analyses of the steady-response suggested that the quantal size did not change dramatically during TBS. Deconvolution of TBS-evoked Ca²⁺ responses revealed a heterogeneous population of synapses differing in their capacity to signal high-frequency information, with an average effective steady-state release rate of 2.6 vesicles synapse^–1 s^–1. To assess how the optically determined release rates compare with population measures we analysed the rate of decay of peak EPSCs during train stimulation. From these studies, we estimated a unitary vesicular replenishment rate of 0.02 s^–1, which corresponds to an average release rate of 0.8–2 vesicles s^–1 at individual synapses. Additionally, extracellular recordings from single Schaffer collaterals revealed that spikes propagate reliably during TBS. Hence, during high-frequency activity, Schaffer collaterals conduct spikes with high fidelity, but release quanta with relatively lower efficiency, leaving NMDA receptor function largely intact and synapse specific. Heterogeneity in release rates between synapses suggests that similar patterns of presynaptic action potentials could trigger different forms of plasticity at individual synapses.

(Received 13 February 2007; accepted after revision 25 April 2007; first published online 26 April 2007)
Corresponding author T. H. Murphy: 2255 Wesbrook Mall, Vancouver, British Columbia, Canada V6T 1Z3. Email: thmurphy{at}interchange.ubc.ca

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