Mechanisms of long-term potentiation expressed by NMDA receptors at hippocampal CA3-CA1 synapses
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1
University of Toronto, Department of Physiology, Canada
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2
University of Western Ontario, Robarts Research Institute, Canada
Background: Long-term potentiation (LTP) of the excitatory synapses, made between the pyramidal neurons of the CA3 and CA1 regions of the hippocampus, serves as a well characterized cellular model of experience driven synaptic plasticity. Enhanced efficacy and expression of AMPA receptors underlies the maintenance of LTP (AMPALTP) but activation of NMDA receptors is required for the induction. It remains unknown whether or not long-term potentiation expressed by NMDARs (NMDALTP) also contributes to AMPALTP.
Method: Whole cell patch clamp recordings were made for CA1 pyramidal neurons in the transverse hippocampal slice. Pharmacologically isolated NMDAEPSCs (-60mV) were evoked following stimulation of the Schaffer/collateral pathway. And NMDALTP was induced by pairing a postsynaptic depolarization (0mV) with low-frequency presynaptic stimulation (1 Hz, 50 pulses).
Results: The NMDALTP did not require release of intracellular Ca2+ via stimulation of mGluR5 receptors but required both NMDARs activation as well as a concomitant elevation of postsynaptic Ca2+. The NMDALTP depended upon activation of either NR2A or NR2B subunit containing NMDARs as well as the subsequent stimulation of protein kinase C (PKC). Similar to AMPALTP, both the induction and expression of NMDALTP was dependent upon activation of Src kinase. Furthermore, the NMDALTP stabilized the maintenance of AMPALTP.
Conclusions: The LTP of NMDARs mediated synaptic transmission provides a Src-dependent positive feedback mechanism which amplifies the NMDARs dependent Ca2+ signal during the induction of LTP.
Therefore the activation of NMDARs is required for the induction of AMPALTP, but the NMDALTP is required for the stabilization of AMPALTP at CA1 synapses.
Conference:
B.R.A.I.N. platform in Physiology poster day 2009, Toronto, ON, Canada, 16 Dec - 16 Dec, 2009.
Presentation Type:
Poster Presentation
Topic:
Poster presentations
Citation:
Li
H,
Jackson
MF,
Yang
K,
Trepanier
C,
Orser
B and
MacDonald
JF
(2009). Mechanisms of long-term potentiation expressed by NMDA receptors at hippocampal CA3-CA1 synapses.
Front. Neurosci.
Conference Abstract:
B.R.A.I.N. platform in Physiology poster day 2009.
doi: 10.3389/conf.neuro.03.2009.17.035
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Received:
17 Dec 2009;
Published Online:
17 Dec 2009.
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Correspondence:
Hong-bin Li, University of Toronto, Department of Physiology, Toronto, Canada, hongbin.li@utoronto.ca