ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
M1-muscarinic receptors promote fear memory consolidation via phospholipase C and the M-current.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- Circuit-selective pharmacological targeting of prefrontal cortex-projecting locus coeruleus neurons drives antinociception.Cell reports · 2025Article
- Article
- PKCδ is an activator of neuronal mitochondrial metabolism that mediates the spacing effect on memory consolidation.bioRxiv : the preprint server for biology · 2024Article
- MPP2 interacts with SK2 to rescue the excitability of glutamatergic neurons in the BLA and facilitate the extinction of conditioned fear in mice.CNS neuroscience & therapeutics · 2024Article
- Potassium channels in animal models of post-traumatic stress disorder: mechanistic and therapeutic implications.Frontiers in cellular neuroscience · 2024Article
- Muscarinic antagonists impair multiple aspects of operant discrimination learning and performance.Neuroscience letters · 2023Article
- Contextual fear response is modulated by M-type K+ channels and is associated with subtle structural changes of the axon initial segment in hippocampal GABAergic neurons.AIMS neuroscience · 2023Article
- Alternative Targets for Modulators of Mitochondrial Potassium Channels.Molecules (Basel, Switzerland) · 2022Review
- Roles of PLCβ, PIPJournal of cellular physiology · 2022Article
- Neuropharmacology of Cevimeline and Muscarinic Drugs-Focus on Cognition and Neurodegeneration.International journal of molecular sciences · 2021Review
- Beneficial effect of retigabine on memory in rats receiving ethanol.Pharmacological reports : PR · 2021Article
- Neuromodulation of Persistent Activity and Working Memory Circuitry in Primate Prefrontal Cortex by Muscarinic Receptors.Frontiers in neural circuits · 2021Review
- Kv7 Channels and Excitability Disorders.Handbook of experimental pharmacology · 2021Article
- Hippocampal knockdown of α2 nicotinic or M1 muscarinic acetylcholine receptors in C57BL/6J male mice impairs cued fear conditioning.Genes, brain, and behavior · 2020Article
- Inhibition of M/KFrontiers in molecular neuroscience · 2020Article
- MBiological psychiatry · 2019Article
- Role of Thioredoxin 1 in Impaired Renal Sodium Excretion of hDJournal of the American Heart Association · 2019Article
- Norepinephrine Induces PTSD-Like Memory ImpairmentsFrontiers in behavioral neuroscience · 2019Article
- Physiological roles of CNS muscarinic receptors gained from knockout mice.Neuropharmacology · 2018Review
- XE991 and Linopirdine Are State-Dependent Inhibitors for Kv7/KCNQ Channels that Favor Activated Single Subunits.The Journal of pharmacology and experimental therapeutics · 2017Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Neuromodulators released during and after a fearful experience promote the consolidation of long-term memory for that experience. Because overconsolidation may contribute to the recurrent and intrusive memories of post-traumatic stress disorder, neuromodulatory receptors provide a potential pharmacological target for prevention. Stimulation of muscarinic receptors promotes memory consolidation in several conditioning paradigms, an effect primarily associated with the M1 receptor (M1R). However, neither inhibiting nor genetically disrupting M1R impairs the consolidation of cued fear memory. Using the M1R agonist cevimeline and antagonist telenzepine, as well as M1R knock-out mice, we show here that M1R, along with β2-adrenergic (β2AR) and D5-dopaminergic (D5R) receptors, regulates the consolidation of cued fear memory by redundantly activating phospholipase C (PLC) in the basolateral amygdala (BLA). We also demonstrate that fear memory consolidation in the BLA is mediated in part by neuromodulatory inhibition of the M-current, which is conducted by KCNQ channels and is known to be inhibited by muscarinic receptors. Manipulating the M-current by administering the KCNQ channel blocker XE991 or the KCNQ channel opener retigabine reverses the effects on consolidation caused by manipulating β2AR, D5R, M1R, and PLC. Finally, we show that cAMP and protein kinase A (cAMP/PKA) signaling relevant to this stage of consolidation is upstream of these neuromodulators and PLC, suggesting an important presynaptic role for cAMP/PKA in consolidation. These results support the idea that neuromodulatory regulation of ion channel activity and neuronal excitability is a critical mechanism for promoting consolidation well after acquisition has occurred.
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Registered trials
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 Socratic graph.