HCN1 channels constrain DHPG-induced LTD at hippocampal Schaffer collateral-CA1 synapses

Tursonjan Tokay, Marco Rohde, Sabine Krabbe, Mirko Rehberg, Roland A. Bender, Rüdiger Köhling, Timo Kirschstein

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


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 μM) 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 μM, 10 min) was significantly enhanced when HCN channels were blocked by ZD7288 (10 μM) 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.

Original languageEnglish
Pages (from-to)769-776
Number of pages8
JournalLearning and Memory
Issue number12
Publication statusPublished - Dec 2009

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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