| Abstract No.: | A-B1030 |
| Country: | Canada |
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| Title: | POSTSYNAPTIC SIGNALS MEDIATING INDUCTION OF LONG-TERM SYNAPTIC DEPRESSION IN THE ENTORHINAL CORTEX. |
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| Authors/Affiliations: | 1 Stephen Glasgow*; 1 Said Kourrich; 1 Douglas Caruana; 1 Andrew Chapman;
1 Concordia University, Montreal, QC, Canada
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| Content: | Objective: The entorhinal cortex receives a large projection from the piriform (olfactory) cortex, and synaptic plasticity in this pathway may affect how olfactory information is processed. Long-lasting changes in the strength of synaptic inputs to the entorhinal cortex may also modulate the integration of multi-modal sensory inputs within the entorhinal cortex, and contribute to mnemonic processes mediated by the entorhinal cortex. The cellular mechanisms that mediate the induction and expression of long-term synaptic depression (LTD) in the entorhinal cortex, however, have not been fully determined. Materials and Methods: A stimulation electrode was placed to activate layer I afferents to layer II, and whole-cell recordings were obtained from layer II entorhinal cortex neurons. LTD was induced using 900 pairs of stimulation pulses delivered a frequency of 1 Hz for 15 min, and evoked postsynaptic potentials (EPSPs) were monitored 10 min before, and 30 min after induction of long-term synaptic depression (LTD). Pharmacological agents were used to assess the dependence of LTD on NMDA receptor activation, Ca2+ currents, and activation of protein phosphatases. Results: As previously reported, LTD in the entorhinal cortex was dependent on NMDA receptor activation, as bath application of APV (50 µM) blocked LTD induction. The role of postsynaptic Ca2+ was assessed by including the Ca2+ chelator BAPTA (10 mM) in the recording electrode solution. Intracellular BAPTA blocked LTD induction, suggesting that postsynaptic increases in intracellular Ca2+ are necessary for LTD induction. The role of the calmodulin-dependent protein phosphatase calcineurin (PP2b) in LTD induction was tested by either pre-exposure of slices to cyclosporine A (250 µM) or by including the selective PP2b blocker FK506 (50 µM) in the recording solution. Induction of LTD was blocked when FK506 was including in the intracellular solution, but was not blocked by cyclosporine A. High doses of okadaic acid (1.0 µM), which blocks protein phosphatases 1 and 2a, also blocked LTD induction, suggesting that activation of protein phosphatase 1 contributes to mechanisms of LTD in the entorhinal cortex. Conclusions: The present study has used a repetitive paired-pulse stimulation pattern to induce LTD in layer I inputs to layer II cells of the entorhinal cortex, and has determined that postsynaptic NMDA receptor activation and increases in intracellular Ca2+ are required for LTD induction. Results also indicate that calcineurin-dependent activation of protein phosphatase 1 contributes to the expression of LTD in these cells. These mechanisms likely mediate synaptic depression effects in the entorhinal cortex that may contribute to short- and long-term mnemonic function. |
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