ArticleProceedings of the National Academy of Sciences of the United States of America2013
Cholinergic signaling in the hippocampus regulates social stress resilience and anxiety- and depression-like behavior.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers, 2 of them syntheses that pooled it.
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Who cites it
189 citing papers in PubMed, 2 syntheses or guidelines pooled it, 367 citations in OpenAlex.
- Cholinergic system in schizophrenia: A systematic review and meta-analysis.Molecular psychiatry · 2025Pooled it
- Integrating Forensic Autopsies with Proteomic Profiling for Suicide Risk Assessment: A Comprehensive Review of Literature.Current neuropharmacology · 2025Pooled it
- DNMT1 function in cortical PV interneurons modulates cortical network activity, mood disorder‑related behavior, and perineuronal nets.Communications biology · 2026Article
- Dysregulation of local inhibitory inputs onto laterodorsal tegmental nucleus cholinergic neurons drives depression-like behaviors in mice.Molecular psychiatry · 2026Article
- Sertraline and Escitalopram But Not Other Antidepressants Increase Acetylcholinesterase ActivityAnnals of neurosciences · 2026Article
- Excitatory cholecystokinin neurons in the CA3 area regulate the navigation learning and neuroplasticity.eLife · 2026Article
- Transcriptomic investigation of agonistic behaviors of boxer shrimps (Stenopus species): insights into the potential neural signaling roles of dopamine and acetylcholine.BMC genomics · 2026Article
- Multiplexed changes in synaptic transmission underlie stress-induced reduction of persistent firing in the parietal cortex.Progress in neurobiology · 2026Article
- Article
- Altered acetylcholine modulations and corticoaccumbal pathway in P11-linked social dysfunction.Molecular psychiatry · 2026Article
- 6-Gingerol ameliorates high-fat, high-sucrose diet-induced metabolic dysfunction and depressive-like behaviors by attenuating neuroinflammation and oxidative stress.Metabolic brain disease · 2026Article
- The hippocampus as a central hub in ketamine's antidepressant action: from molecules to circuit rewiring.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- mPFC Synaptosome Proteomics Reveals Novel Pathways and Muscarinic Receptor Changes in a Learned Helplessness Mouse Model.bioRxiv : the preprint server for biology · 2026Article
- Adult-onset hippocampal α7 nicotinic acetylcholine receptor loss rapidly drives Alzheimer-like neuropathology in mice.Frontiers in pharmacology · 2026Article
- Anxiolytic and antidepressant effects of astaxanthin: behavioral and mechanistic insights in a rat model.Frontiers in pharmacology · 2026Article
- Fetal programming by the parental microbiome of offspring behavior, and DNA methylation and gene expression within the hippocampus.Microbiome · 2025Article
- Review
- A Cross-Generational Methylomic Signature of Infant Maltreatment in Newborn Rhesus Macaques.Biological psychiatry · 2025Article
- 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) modulates biochemical and behavioral adaptations during the early developmental stage of a post-traumatic stress disorder (PTSD) model in mice.Metabolic brain disease · 2025Article
- Real-Time In Vivo Monitoring of Cholinergic Neurotransmission in the Mouse Brain Using a Microelectrochemical Choline Biosensor.The European journal of neuroscience · 2025Article
129 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Symptoms of depression can be induced in humans through blockade of acetylcholinesterase (AChE) whereas antidepressant-like effects can be produced in animal models and some clinical trials by limiting activity of acetylcholine (ACh) receptors. Thus, ACh signaling could contribute to the etiology of mood regulation. To test this hypothesis, we administered the AChE inhibitor physostigmine to mice and demonstrated an increase in anxiety- and depression-like behaviors that was reversed by administration of nicotinic or muscarinic antagonists. The behavioral effects of physostigmine were also reversed by administration of the selective serotonin reuptake inhibitor fluoxetine. Administration of fluoxetine also increased AChE activity throughout the brain, with the greatest change in the hippocampus. To determine whether cholinergic signaling in the hippocampus could contribute to the systemic effects of cholinergic drugs, we infused physostigmine or virally delivered shRNAs targeting AChE into the hippocampus. Both pharmacological and molecular genetic decreases in hippocampal AChE activity increased anxiety- and depression-like behaviors and decreased resilience to repeated stress in a social defeat paradigm. The behavioral changes due to shRNA-mediated knockdown of AChE were rescued by coinfusion of an shRNA-resistant AChE transgene into the hippocampus and reversed by systemic administration of fluoxetine. These data demonstrate that ACh signaling in the hippocampus promotes behaviors related to anxiety and depression. The sensitivity of these effects to fluoxetine suggests that shRNA-mediated knockdown of hippocampal AChE represents a model for anxiety- and depression-like phenotypes. Furthermore, abnormalities in the cholinergic system may be critical for the etiology of mood disorders and could represent an endophenotype of depression.
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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.