ArticleScience translational medicine2021
Hippocampal cAMP regulates HCN channel function on two time scales with differential effects on animal behavior.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery.Biomedicines · 2026Review
- Dorsal CA1 projections to nucleus accumbens and lateral septum differentially regulate social and locomotor behavior.Cerebral cortex (New York, N.Y. : 1991) · 2026Article
- Hyperpolarization-Activated Channel 1 Modulates Resilience and Susceptibility to Social Avoidance Induced by Witnessing Social Defeat Stress.Biological psychiatry · 2025Article
- Hippocampal dorsal CA1: Functional connectivity and role in HCN channelopathies in affective diseases and epilepsy.IBRO neuroscience reports · 2025Article
- HCN channels in the lateral habenula regulate pain and comorbid depressive-like behaviors in mice.CNS neuroscience & therapeutics · 2024Article
- A Molecular Framework for Delirium.The Neurohospitalist · 2024Review
- Context is key: glucocorticoid receptor and corticosteroid therapeutics in outcomes after traumatic brain injury.Frontiers in cellular neuroscience · 2024Review
- Characterization of hyperpolarization-activated cyclic nucleotide-gated channels in oligodendrocytes.Frontiers in cellular neuroscience · 2024Article
- cAMP-mediated upregulation of HCN channels in VTA dopamine neurons promotes cocaine reinforcement.Molecular psychiatry · 2023Article
- GPCR-mediated calcium and cAMP signaling determines psychosocial stress susceptibility and resiliency.Science advances · 2023Article
- Discovery of a small-molecule inhibitor of the TRIP8b-HCN interaction with efficacy in neurons.The Journal of biological chemistry · 2022Article
- Sex- and estrous-cycle dependent dorsal hippocampal phosphoproteomic changes induced by low-dose ketamine.Scientific reports · 2022Article
- Regulation of HCN Channels by Protein Interactions.Frontiers in physiology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Hyperpolarization-activated cyclic nucleotide–gated (HCN) channels regulate neuronal excitability and represent a possible therapeutic target for major depressive disorder (MDD). These channels are regulated by intracellular cyclic adenosine monophosphate (cAMP). However, the relationship between cAMP signaling and the influence of HCN channels on behavior remains opaque. In this study, we investigated the role of hippocampal cAMP signaling on behavior using chemogenetic technology in mice. Acutely increasing cAMP limited spatial memory and motivated behavior by increasing HCN function. However, chronically elevated cAMP limited surface trafficking of HCN channels by disrupting the interaction between HCN and tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b), an auxiliary subunit. Chronically increased cAMP in the dorsal hippocampus was also sufficient to rescue cognitive deficits induced by chronic stress in mice. These results reveal a behaviorally relevant form of regulation of HCN channel surface expression that has potential as a therapeutic target for cognitive deficits related to chronic stress.
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