ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Prefrontal cortex HCN1 channels enable intrinsic persistent neural firing and executive memory function.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 92 citations in OpenAlex.
- Multimodal evidence for a mechanistic model of working memory deficits in schizophrenia.medRxiv : the preprint server for health sciences · 2026Article
- Guanfacine and HCN channels: bridging neuroinflammation and prefrontal cortex function in autism spectrum disorder.Frontiers in molecular neuroscience · 2026Review
- Article
- Functional implications of atypical action potential generation in the (patho)physiological brain: from developmental program to glioma.Frontiers in neural circuits · 2026Review
- Common Genomic and Proteomic Alterations Related to Disturbed Neural Oscillatory Activity in Schizophrenia.International journal of molecular sciences · 2025Review
- Cell-type-specific cholinergic control of granular retrosplenial cortex with implications for angular velocity coding across brain states.Progress in neurobiology · 2025Article
- Harnessing a noncanonical vestibular input in the head-direction network to rectify age-related navigational deficits.Nature aging · 2025Article
- Increased Complement C4 in a Sparse Neuronal Subset Induces Network-Wide Transcriptomic Alterations in the Prefrontal Cortex.bioRxiv : the preprint server for biology · 2025Article
- Interneuron-selective HCN channel knockdown in prelimbic cortex of female rats mimics effects of chronic ethanol exposure.Alcohol (Fayetteville, N.Y.) · 2024Article
- Activity-Dependent Ectopic Spiking in Parvalbumin-Expressing Interneurons of the Neocortex.eNeuro · 2024Article
- Effect of size on expression of bistability in mouse spinal motoneurons.Journal of neurophysiology · 2024Article
- Interaction Between HCN and Slack Channels Regulates mPFC Pyramidal Cell Excitability in Working Memory Circuits.Molecular neurobiology · 2024Article
- Localization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer's disease.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Striatum-projecting prefrontal cortex neurons support working memory maintenance.Nature communications · 2023Article
- Temporal disparity of action potentials triggered in axon initial segments and distal axons in the neocortex.Science advances · 2023Article
- Article
- Cognitive neuroscience perspective on memory: overview and summary.Frontiers in human neuroscience · 2023Article
- Genetic Influences on Cognitive Dysfunction in Schizophrenia.Current topics in behavioral neurosciences · 2023Article
- Evidence for the contribution of HCN1 gene polymorphism (rs1501357) to working memory at both behavioral and neural levels in schizophrenia patients and healthy controls.Schizophrenia (Heidelberg, Germany) · 2022Article
- Article
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
Abstract
In many cortical neurons, HCN1 channels are the major contributors to Ih, the hyperpolarization-activated current, which regulates the intrinsic properties of neurons and shapes their integration of synaptic inputs, paces rhythmic activity, and regulates synaptic plasticity. Here, we examine the physiological role of Ih in deep layer pyramidal neurons in mouse prefrontal cortex (PFC), focusing on persistent activity, a form of sustained firing thought to be important for the behavioral function of the PFC during working memory tasks. We find that HCN1 contributes to the intrinsic persistent firing that is induced by a brief depolarizing current stimulus in the presence of muscarinic agonists. Deletion of HCN1 or acute pharmacological blockade of Ih decreases the fraction of neurons capable of generating persistent firing. The reduction in persistent firing is caused by the membrane hyperpolarization that results from the deletion of HCN1 or Ih blockade, rather than a specific role of the hyperpolarization-activated current in generating persistent activity. In vivo recordings show that deletion of HCN1 has no effect on up states, periods of enhanced synaptic network activity. Parallel behavioral studies demonstrate that HCN1 contributes to the PFC-dependent resolution of proactive interference during working memory. These results thus provide genetic evidence demonstrating the importance of HCN1 to intrinsic persistent firing and the behavioral output of the PFC. The causal role of intrinsic persistent firing in PFC-mediated behavior remains an open question.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.