ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016
AMPK Signaling in the Dorsal Hippocampus Negatively Regulates Contextual Fear Memory Formation.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 44 citations in OpenAlex.
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- Anxiolytic effect of antidiabetic metformin is mediated by AMPK activation in mPFC inhibitory neurons.Molecular psychiatry · 2023Article
- A nexus of lipid andFrontiers in endocrinology · 2022Review
- Acute Nicotine Treatment Alleviates LPS-Induced Impairment of Fear Memory Reconsolidation Through AMPK Activation and CRTC1 Upregulation in Hippocampus.The international journal of neuropsychopharmacology · 2020Article
- UPF2 leads to degradation of dendritically targeted mRNAs to regulate synaptic plasticity and cognitive function.Molecular psychiatry · 2020Article
- Metformin Enhances Excitatory Synaptic Transmission onto Hippocampal CA1 Pyramidal Neurons.Brain sciences · 2020Article
- Cognitive Decline and Modulation of Alzheimer's Disease-Related Genes After Inhibition of MicroRNA-101 in Mouse Hippocampal Neurons.Molecular neurobiology · 2020Article
- Systemic immunization with altered myelin basic protein peptide produces sustained antidepressant-like effects.Molecular psychiatry · 2020Article
- Kinase network dysregulation in a human induced pluripotent stem cell model of DISC1 schizophrenia.Molecular omics · 2019Article
- Neuronal AMP-activated protein kinase hyper-activation induces synaptic loss by an autophagy-mediated process.Cell death & disease · 2019Article
- Pavlovian Olfactory Fear Conditioning: Its Neural Circuity and Importance for Understanding Clinical Fear-Based Disorders.Frontiers in molecular neuroscience · 2019Review
- Traumatic Stress Produces Delayed Alterations of Synaptic Plasticity in Basolateral Amygdala.Frontiers in psychology · 2019Article
- Protein kinase Mζ in medial prefrontal cortex mediates depressive-like behavior and antidepressant response.Molecular psychiatry · 2018Article
- Rescue of Learning and Memory Deficits in the Human Nonsyndromic Intellectual Disability Cereblon Knock-Out Mouse Model by Targeting the AMP-Activated Protein Kinase-mTORC1 Translational Pathway.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Uncoupling DAPK1 from NMDA receptor GluN2B subunit exerts rapid antidepressant-like effects.Molecular psychiatry · 2018Article
- Intermittent metabolic switching, neuroplasticity and brain health.Nature reviews. Neuroscience · 2018Review
- Effect of Ketamine on LTP and NMDAR EPSC in Hippocampus of the Chronic Social Defeat Stress Mice Model of Depression.Frontiers in behavioral neuroscience · 2018Article
- Bumetanide treatment during early development rescues maternal separation-induced susceptibility to stress.Scientific reports · 2017Article
- Calpain-GRIP Signaling in Nucleus Accumbens Core Mediates the Reconsolidation of Drug Reward Memory.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Both the formation of long-term memory (LTM) and dendritic spine growth that serves as a physical basis for the long-term storage of information require de novo protein synthesis. Memory formation also critically depends on transcription. Adenosine monophosphate-activated protein kinase (AMPK) is a transcriptional regulator that has emerged as a major energy sensor that maintains cellular energy homeostasis. However, still unknown is its role in memory formation. In the present study, we found that AMPK is primarily expressed in neurons in the hippocampus, and then we demonstrated a time-dependent decrease in AMPK activity and increase in mammalian target of rapamycin complex 1 (mTORC1) activity after contextual fear conditioning in the CA1 but not CA3 area of the dorsal hippocampus. Using pharmacological methods and adenovirus gene transfer to bidirectionally regulate AMPK activity, we found that increasing AMPK activity in the CA1 impaired the formation of long-term fear memory, and decreasing AMPK activity enhanced fear memory formation. These findings were associated with changes in the phosphorylation of AMPK and p70s6 kinase (p70s6k) and expression of BDNF and membrane GluR1 and GluR2 in the CA1. Furthermore, the prior administration of an mTORC1 inhibitor blocked the enhancing effect of AMPK inhibition on fear memory formation, suggesting that this negative regulation of contextual fear memory by AMPK in the CA1 depends on the mTORC1 signaling pathway. Finally, we found that AMPK activity regulated hippocampal spine growth associated with memory formation. In summary, our results indicate that AMPK is a key negative regulator of plasticity and fear memory formation.
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