ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Nicotine blocks the hyperpolarization-activated current Ih and severely impairs the oscillatory behavior of oriens-lacunosum moleculare interneurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Deciphering the peculiarities of cell types in the septum.Neuroscience · 2025Article
- The Theta Rhythm of the Hippocampus: From Neuronal and Circuit Mechanisms to Behavior.Frontiers in cellular neuroscience · 2021Article
- Neuromodulation of Hippocampal-Prefrontal Cortical Synaptic Plasticity and Functional Connectivity: Implications for Neuropsychiatric Disorders.Frontiers in cellular neuroscience · 2021Review
- The HCN Channel Blocker ZD7288 Induces Emesis in the Least Shrew (Frontiers in pharmacology · 2021Article
- Ion Channel Contributions to Morphological Development: Insights From the Role of Kir2.1 in Bone Development.Frontiers in molecular neuroscience · 2020Review
- Characterization of drug binding within the HCN1 channel pore.Scientific reports · 2019Article
- Hippocampal GABAergic Inhibitory Interneurons.Physiological reviews · 2017Review
- Revisiting the Lamotrigine-Mediated Effect on Hippocampal GABAergic Transmission.International journal of molecular sciences · 2016Article
- HCN Channels Modulators: The Need for Selectivity.Current topics in medicinal chemistry · 2016Review
- Pin1-dependent signalling negatively affects GABAergic transmission by modulating neuroligin2/gephyrin interaction.Nature communications · 2014Article
- Age-related changes in nicotine response of cholinergic and non-cholinergic laterodorsal tegmental neurons: implications for the heightened adolescent susceptibility to nicotine addiction.Neuropharmacology · 2014Article
- Modulation of HCN channels in lateral septum by nicotine.Neuropharmacology · 2014Article
- cAMP control of HCN2 channel Mg2+ block reveals loose coupling between the cyclic nucleotide-gating ring and the pore.PloS one · 2014Article
- Reexposure to nicotine during withdrawal increases the pacemaking activity of cholinergic habenular neurons.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Regulation of epileptiform discharges in rat neocortex by HCN channels.Journal of neurophysiology · 2013Article
- Developmental nicotine exposure alters AMPA neurotransmission in the hypoglossal motor nucleus and pre-Botzinger complex of neonatal rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- In hippocampal oriens interneurons anti-Hebbian long-term potentiation requires cholinergic signaling via α7 nicotinic acetylcholine receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Developmental regulation of GABAergic signalling in the hippocampus of neuroligin 3 R451C knock-in mice: an animal model of Autism.Frontiers in cellular neuroscience · 2013Article
- Postnatal maturation of somatostatin-expressing inhibitory cells in the somatosensory cortex of GIN mice.Frontiers in neural circuits · 2012Article
- Exploring HCN channels as novel drug targets.Nature reviews. Drug discovery · 2011Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the brain, high cognitive functions are encoded by coherent network oscillations. Key players are inhibitory interneurons that, by releasing GABA into principal cells, pace targeted cells. Among these, oriens-lacunosum moleculare (O-LM) interneurons that provide a theta frequency patterned output to distal dendrites of pyramidal cells are endowed with HCN channels responsible for the slowly activating inwardly rectifying Ih current and their pacemaking activity. Here we show that, in transgenic mice expressing EGFP (enhanced green fluorescent protein) in a subset of stratum oriens somatostatin-containing interneurons that mostly comprise O-LM cells, nicotine, the active component of tobacco, reduced Ih and the oscillatory behavior of O-LM interneurons. In cells hyperpolarized at -90 mV, nicotine suppressed the theta resonance in the same way as ZD 7288 (4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride), a selective blocker of Ih. Nicotine blocked Ih in a concentration-dependent way with an EC50 of 62 nm. Similar effects were produced by epibatidine, a structural analog of nicotine. The effects of nicotine and epibatidine were independent on nicotinic ACh receptor (nAChR) activation because they persisted in the presence of nAChR antagonists. Furthermore, nicotine slowed down the interspike depolarizing slope and the firing rate, thus severely disrupting the oscillatory behavior of O-LM cells. Molecular modeling suggests that, similarly to ZD 7288, nicotine and epibatidine directly bind to the inner pore of the HCN channels. It is therefore likely that nicotine severely influences rhythmogenesis and high cognitive functions in smokers.
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