HCN1 channels constrain DHPG-induced LTD at hippocampal Schaffer collateral-CA1 synapses.
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HCN1 channels constrain DHPG-induced LTD at hippocampal Schaffer collateral-CA1 synapses. / Tokay, Tursonjan; Marco, Rohde; Krabbe, Sabine; Rehberg, Mirko; Bender, Roland; Köhling, Rüdiger; Kirschstein, Timo.
In: LEARN MEMORY, Vol. 16, No. 12, 12, 2009, p. 769-776.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - HCN1 channels constrain DHPG-induced LTD at hippocampal Schaffer collateral-CA1 synapses.
AU - Tokay, Tursonjan
AU - Marco, Rohde
AU - Krabbe, Sabine
AU - Rehberg, Mirko
AU - Bender, Roland
AU - Köhling, Rüdiger
AU - Kirschstein, Timo
PY - 2009
Y1 - 2009
N2 - HCN channels play a fundamental role in determining resting membrane potential and regulating synaptic function. Here, we investigated the involvement of HCN channels in basal synaptic transmission and long-term depression (LTD) at the Schaffer collateral-CA1 synapse. Bath application of the HCN channel blocker ZD7288 (10 microM) caused a significant increase in synaptic transmission that was due to an enhancement in AMPA receptor-mediated excitatory postsynaptic potentials. This enhancement was accompanied by a significant decrease in the paired-pulse ratio (PPR), suggesting a presynaptic mechanism. Experiments with the irreversible use-dependent NMDA receptor blocker MK-801 showed that ZD7288 led to an increase in glutamate release probability. LTD induced by brief application of (RS)-3,5-dihydroxyphenylglycine (DHPG, 100 microM, 10 min) was significantly enhanced when HCN channels were blocked by ZD7288 (10 microM) prior to DHPG application. Moreover, the concomitant increase in PPR after DHPG-induced LTD was significantly larger than without ZD7288 bath application. Conversely, ZD7288 application after DHPG washout did not alter DHPG-LTD. A significant enhancement of DHPG-LTD was also observed in HCN1-deficient mice as compared with wild types. However, LTD induced by low-frequency stimulation (LFS) remained unaltered in HCN1-deficient mice, suggesting a differential effect of HCN1 channels on synaptic plasticity constraining DHPG-LTD, but not LFS-LTD.
AB - HCN channels play a fundamental role in determining resting membrane potential and regulating synaptic function. Here, we investigated the involvement of HCN channels in basal synaptic transmission and long-term depression (LTD) at the Schaffer collateral-CA1 synapse. Bath application of the HCN channel blocker ZD7288 (10 microM) caused a significant increase in synaptic transmission that was due to an enhancement in AMPA receptor-mediated excitatory postsynaptic potentials. This enhancement was accompanied by a significant decrease in the paired-pulse ratio (PPR), suggesting a presynaptic mechanism. Experiments with the irreversible use-dependent NMDA receptor blocker MK-801 showed that ZD7288 led to an increase in glutamate release probability. LTD induced by brief application of (RS)-3,5-dihydroxyphenylglycine (DHPG, 100 microM, 10 min) was significantly enhanced when HCN channels were blocked by ZD7288 (10 microM) prior to DHPG application. Moreover, the concomitant increase in PPR after DHPG-induced LTD was significantly larger than without ZD7288 bath application. Conversely, ZD7288 application after DHPG washout did not alter DHPG-LTD. A significant enhancement of DHPG-LTD was also observed in HCN1-deficient mice as compared with wild types. However, LTD induced by low-frequency stimulation (LFS) remained unaltered in HCN1-deficient mice, suggesting a differential effect of HCN1 channels on synaptic plasticity constraining DHPG-LTD, but not LFS-LTD.
M3 - SCORING: Zeitschriftenaufsatz
VL - 16
SP - 769
EP - 776
JO - LEARN MEMORY
JF - LEARN MEMORY
SN - 1072-0502
IS - 12
M1 - 12
ER -
