ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2012
Muscarinic receptors modulate the intrinsic excitability of infralimbic neurons and consolidation of fear extinction.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 79 citations in OpenAlex.
- Cholinergic Modulation of Exposure Disrupts Hippocampal Processes and Augments Extinction: Proof-of-Concept Study With Social Anxiety Disorder.Biological psychiatry · 2019Trial
- Chemogenetic activation of the medial prefrontal cortex alleviates the impaired extinction of fear memory through the increase in the binding of EGR1 and TET1 in an animal model of PTSD.Psychopharmacology · 2026Article
- Mild Traumatic Brain Injury Impairs Fear Extinction and Network Excitability in the Infralimbic Cortex.Journal of neurotrauma · 2025Article
- Infralimbic Projections to the Substantia Innominata-Ventral Pallidum Constrain Defensive Behavior during Extinction Learning.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Nighttime-specific differential gene expression in suprachiasmatic nucleus and habenula is associated with resilience to chronic social stress.Translational psychiatry · 2024Article
- Infralimbic activity during REM sleep facilitates fear extinction memory.Current biology : CB · 2024Article
- Basal forebrain cholinergic systems as circuits through which traumatic stress disrupts emotional memory regulation.Neuroscience and biobehavioral reviews · 2024Review
- Neural circuits for the adaptive regulation of fear and extinction memory.Frontiers in behavioral neuroscience · 2024Review
- 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
- Update on neurobiological mechanisms of fear: illuminating the direction of mechanism exploration and treatment development of trauma and fear-related disorders.Frontiers in behavioral neuroscience · 2023Review
- Sex differences in acetylcholinesterase modulation during spatial and fear memory extinction in the amygdala; an animal study in the single prolonged stress model of PTSD.Research in pharmaceutical sciences · 2022Article
- Infralimbic cortex functioning across motivated behaviors: Can the differences be reconciled?Neuroscience and biobehavioral reviews · 2021Review
- Understanding the dynamic and destiny of memories.Neuroscience and biobehavioral reviews · 2021Review
- Plasticity of GluN1 at Ventral Hippocampal Synapses in the Infralimbic Cortex.Frontiers in synaptic neuroscience · 2021Article
- Cholinergic neurotransmission in the basolateral amygdala during cued fear extinction.Neurobiology of stress · 2020Article
- Learning-induced intrinsic and synaptic plasticity in the rodent medial prefrontal cortex.Neurobiology of learning and memory · 2020Review
- Regulation of intrinsic excitability: Roles for learning and memory, aging and Alzheimer's disease, and genetic diversity.Neurobiology of learning and memory · 2019Review
- Sex differences in fear extinction.Neuroscience and biobehavioral reviews · 2019Review
- MBiological psychiatry · 2019Article
- Lack of experience-dependent intrinsic plasticity in the adolescent infralimbic medial prefrontal cortex.Synapse (New York, N.Y.) · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
There is considerable interest in identifying pharmacological compounds that could be used to facilitate fear extinction. Recently, we showed that the modulation of M-type K(+) channels regulates the intrinsic excitability of infralimbic (IL) neurons and fear expression. As muscarinic acetylcholine receptors inhibit M-type K(+) channels, cholinergic inputs to IL may have an important role in controlling IL excitability and, thereby, fear expression and extinction. To test this model, we combined whole-cell patch-clamp electrophysiology and auditory fear conditioning. In prefrontal brain slices, muscarine enhanced the intrinsic excitability of IL neurons by reducing the M-current and the slow afterhyperpolarization, resulting in an increased number of spikes with shorter inter-spike intervals. Next, we examined the role of endogenous activation of muscarinic receptors in fear extinction. Systemic injected scopolamine (Scop) (muscarinic receptor antagonist) before or immediately after extinction training impaired recall of extinction 24-h later, suggesting that muscarinic receptors are critically involved in consolidation of extinction memory. Similarly, infusion of Scop into IL before extinction training also impaired recall of extinction 24-h later. Finally, we demonstrated that systemic injections of the muscarinic agonist, cevimeline (Cev), given before or immediately after extinction training facilitated recall of extinction the following day. Taken together, these findings suggest that cholinergic inputs to IL have a critical role in modulating consolidation of fear extinction and that muscarinic agonists such as Cev might be useful for facilitating extinction memory in patients suffering from anxiety disorders.
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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.