ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Migraine mutations impair hippocampal learning despite enhanced long-term potentiation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 55 citations in OpenAlex.
- Transcriptomic Profile Analysis of Brain Tissue in the Absence of Functional TRPM8 Calcium Channel.Biomedicines · 2024Article
- Review
- Models of Trigeminal Activation: Is There an Animal Model of Migraine?Brain sciences · 2024Review
- The genotype-phenotype correlations of theFrontiers in molecular neuroscience · 2023Article
- P2X7R/NLRP3 signaling pathway-mediated pyroptosis and neuroinflammation contributed to cognitive impairment in a mouse model of migraine.The journal of headache and pain · 2022Article
- Attenuated alpha oscillation and hyperresponsiveness reveals impaired perceptual learning in migraineurs.The journal of headache and pain · 2022Article
- Focal Subcortical White Matter Lesions Disrupt Resting State Cortical Interhemispheric Functional Connectivity in Mice.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- Responsivity to light in familial hemiplegic migraine type 1 mutant mice reveals frequency-dependent enhancement of visual network excitability.The European journal of neuroscience · 2021Article
- Nitric oxide role in anxiety-like behavior, memory and cognitive impairments in animal model of chronic migraine.Heliyon · 2020Article
- Two distinct phenotypes, hemiplegic migraine and episodic Ataxia type 2, caused by a novel common CACNA1A variant.BMC neurology · 2020Article
- Sodium Fluctuations in Astroglia and Their Potential Impact on Astrocyte Function.Frontiers in physiology · 2020Review
- Genetic mouse models of migraine.The journal of headache and pain · 2019Review
- Behavioral and cognitive animal models in headache research.The journal of headache and pain · 2019Review
- Mouse Models of Familial Hemiplegic Migraine for Studying Migraine Pathophysiology.Current neuropharmacology · 2019Review
- Impaired Cognitive Performance in Endothelial Nitric Oxide Synthase Knockout Mice After Ischemic Stroke: A Pilot Study.American journal of physical medicine & rehabilitation · 2018Article
- A Systems Neuroscience Approach to Migraine.Neuron · 2018Review
- The Effects of Chronic Stress on Migraine Relevant Phenotypes in Male Mice.Frontiers in cellular neuroscience · 2018Article
- Leaky RyR2 channels unleash a brainstem spreading depolarization mechanism of sudden cardiac death.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Impaired spatial memory and enhanced long-term potentiation in mice with forebrain-specific ablation of the Stim genes.Frontiers in behavioral neuroscience · 2015Article
- Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
To explain cognitive and memory difficulties observed in some familial hemiplegic migraine (FHM) patients, we examined hippocampal neurotransmission and plasticity in knock-in mice expressing the FHM type 1 (FHM1) R192Q gain-of function mutation in the CACNA1A gene that encodes the α1A subunit of neuronal CaV2.1 channels. We determined stimulus intensity-response curves for anterior commissure-evoked hippocampal CA1 field potentials in strata pyramidale and radiatum and assessed neuroplasticity by inducing long-term potentiation (LTP) and long-term depression (LTD) in anesthetized mice in vivo. We also studied learning and memory using contextual fear-conditioning, Morris water maze, and novel object recognition tests. Hippocampal field potentials were significantly enhanced in R192Q mice compared with wild-type controls. Stimulus intensity-response curves were shifted to the left and displayed larger maxima in the mutants. LTP was augmented by twofold in R192Q mice, whereas LTD was unchanged compared with wild-type mice. R192Q mice showed significant spatial memory deficits in contextual fear-conditioning and Morris water maze tests compared with wild-type controls. Novel object recognition was not impaired in R192Q mice; however, mice carrying the more severe S218L CACNA1A mutation showed marked deficits in this test, suggesting a genotype-phenotype relationship. Thus, whereas FHM1 gain-of-function mutations enhance hippocampal excitatory transmission and LTP, learning and memory are paradoxically impaired, providing a possible explanation for cognitive changes detected in FHM. Data suggest that abnormally enhanced plasticity can be as detrimental to efficient learning as reduced plasticity and highlight how genetically enhanced neuronal excitability may impact cognitive function.
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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.