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 journalArticle

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Abstract

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
Volume16
Issue number12
DOIs
Publication statusPublished - Dec 2009
Externally publishedYes

Fingerprint

Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Synapses
Hippocampus
Baths
Synaptic Transmission
Neuronal Plasticity
AMPA Receptors
Dizocilpine Maleate
Excitatory Postsynaptic Potentials
N-Methyl-D-Aspartate Receptors
Membrane Potentials
dihydroxyphenylethylene glycol
Glutamic Acid
ICI D2788

ASJC Scopus subject areas

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

Cite this

Tokay, T., Rohde, M., Krabbe, S., Rehberg, M., Bender, R. A., Köhling, R., & Kirschstein, T. (2009). HCN1 channels constrain DHPG-induced LTD at hippocampal Schaffer collateral-CA1 synapses. Learning and Memory, 16(12), 769-776. https://doi.org/10.1101/lm.1556009

HCN1 channels constrain DHPG-induced LTD at hippocampal Schaffer collateral-CA1 synapses. / Tokay, Tursonjan; Rohde, Marco; Krabbe, Sabine; Rehberg, Mirko; Bender, Roland A.; Köhling, Rüdiger; Kirschstein, Timo.

In: Learning and Memory, Vol. 16, No. 12, 12.2009, p. 769-776.

Research output: Contribution to journalArticle

Tokay, T, Rohde, M, Krabbe, S, Rehberg, M, Bender, RA, Köhling, R & Kirschstein, T 2009, 'HCN1 channels constrain DHPG-induced LTD at hippocampal Schaffer collateral-CA1 synapses', Learning and Memory, vol. 16, no. 12, pp. 769-776. https://doi.org/10.1101/lm.1556009
Tokay, Tursonjan ; Rohde, Marco ; Krabbe, Sabine ; Rehberg, Mirko ; Bender, Roland A. ; Köhling, Rüdiger ; Kirschstein, Timo. / HCN1 channels constrain DHPG-induced LTD at hippocampal Schaffer collateral-CA1 synapses. In: Learning and Memory. 2009 ; Vol. 16, No. 12. pp. 769-776.
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