ArticleFrontiers in behavioral neuroscience2011
Mice Lacking Ras-GRF1 Show Contextual Fear Conditioning but not Spatial Memory Impairments: Convergent Evidence from Two Independently Generated Mouse Mutant Lines.
Article in Frontiers in behavioral neuroscience, 2011. 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, 33 citations in OpenAlex.
- The guanine nucleotide exchange factor RapGEF2 is required for ERK-dependent immediate-early gene (Egr1) activation during fear memory formation.Cellular and molecular life sciences : CMLS · 2024Article
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- IntelliCage: the development and perspectives of a mouse- and user-friendly automated behavioral test system.Frontiers in behavioral neuroscience · 2023Review
- Deciphering the Heterogeneity of the Internal Environment of Hippocampal Neurons during Maturation by Raman Spectroscopy.ACS omega · 2022Article
- Designing animal-friendly behavioral tests for neuroscience research: The importance of an ethological approach.Frontiers in behavioral neuroscience · 2022Article
- Article
- Role of genomic imprinting in mammalian development.Journal of biosciences · 2020Review
- Spatial learning and long-term memory impairments in RasGrf1 KO, Pttg1 KO, and double KO mice.Brain and behavior · 2018Article
- New Perspectives on Genomic Imprinting, an Essential and Multifaceted Mode of Epigenetic Control in the Developing and Adult Brain.Annual review of neuroscience · 2016Review
- Conditional Loss of Arx From the Developing Dorsal Telencephalon Results in Behavioral Phenotypes Resembling Mild Human ARX Mutations.Cerebral cortex (New York, N.Y. : 1991) · 2015Article
- The role of genomic imprinting in biology and disease: an expanding view.Nature reviews. Genetics · 2014Review
- Domain contributions to signaling specificity differences between Ras-guanine nucleotide releasing factor (Ras-GRF) 1 and Ras-GRF2.The Journal of biological chemistry · 2014Article
- Genetic variation of the RASGRF1 regulatory region affects human hippocampus-dependent memory.Frontiers in human neuroscience · 2014Article
- Acquisition of contextual discrimination involves the appearance of a RAS-GRF1/p38 mitogen-activated protein (MAP) kinase-mediated signaling pathway that promotes long term potentiation (LTP).The Journal of biological chemistry · 2013Article
- Neuronal Rho GEFs in synaptic physiology and behavior.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2013Review
- Differential hippocampal gene expression is associated with climate-related natural variation in memory and the hippocampus in food-caching chickadees.Molecular ecology · 2013Article
- Activated Ras as a Therapeutic Target: Constraints on Directly Targeting Ras Isoforms and Wild-Type versus Mutated Proteins.ISRN oncology · 2013Review
- Age-related increase in amyloid plaque burden is associated with impairment in conditioned fear memory in CRND8 mouse model of amyloidosis.Alzheimer's research & therapy · 2012Article
- Neuronal signaling and behavior.Frontiers in behavioral neuroscience · 2012Article
- Ras-ERK Signaling in Behavior: Old Questions and New Perspectives.Frontiers in behavioral neuroscience · 2011Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ras-GRF1 is a neuronal specific guanine exchange factor that, once activated by both ionotropic and metabotropic neurotransmitter receptors, can stimulate Ras proteins, leading to long-term phosphorylation of downstream signaling. The two available reports on the behavior of two independently generated Ras-GRF1 deficient mouse lines provide contrasting evidence on the role of Ras-GRF1 in spatial memory and contextual fear conditioning. These discrepancies may be due to the distinct alterations introduced in the mouse genome by gene targeting in the two lines that could differentially affect expression of nearby genes located in the imprinted region containing the Ras-grf1 locus. In order to determine the real contribution of Ras-GRF1 to spatial memory we compared in Morris Water Maze learning Brambilla's mice with a third mouse line (GENA53) in which a non-sense mutation was introduced in the Ras-GRF1 coding region without additional changes in the genome and we found that memory in this task is normal. Also, we measured both contextual and cued fear conditioning, which were previously reported to be affected in Brambilla's mice, and we confirmed that contextual learning but not cued conditioning is impaired in both mouse lines. In addition, we also tested both lines for the first time in conditioned place aversion in the Intellicage, an ecological and remotely controlled behavioral test, and we observed normal learning. Finally, based on previous reports of other mutant lines suggesting that Ras-GRF1 may control body weight, we also measured this non-cognitive phenotype and we confirmed that both Ras-GRF1 deficient mutants are smaller than their control littermates. In conclusion, we demonstrate that Ras-GRF1 has no unique role in spatial memory while its function in contextual fear conditioning is likely to be due not only to its involvement in amygdala functions but possibly to some distinct hippocampal connections specific to contextual learning.
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