Extinction and reacquisition of a fear-motivated memory require activity of the Src family of tyrosine kinases in the CA1 region of the hippocampus
Abstract
Evidences indicate that extinction represents a NMDA receptor (NMDAr)-dependent learning rather than erasure of previously stored information. Several members of the Src family of tyrosine kinases are activated by stimulation of the NMDAr and are involved in both induction of hippocampal long-term potentiation and consolidation of hippocampal-dependent, NMDAr-sensitive, memories. Here we analyzed the role of the Src family within the CA1 region of the hippocampus in extinction and reacquisition of the memory for step-down, inhibitory avoidance learning task (IA). Rats trained in IA were submitted to 5 daily extinction sessions during which the avoidance response was elicited in the absence of the unconditioned stimulus. Immediately or 180 min after each extinction session animals received intra-CA1 infusions of either 0.1% DMSO, the Src-family inhibitor PP2 or its inactive analog, PP3. PP2 blocked extinction of the IA response which was otherwise evident in DMSO and PP3-treated animals. After being submitted to a new training session the animals reacquired the avoidance response; however, they failed to do so if they received intra-CA1 infusions of PP2 immediately following retraining. Our results indicate that, like the original learning, extinction and reacquisition of the IA response require activity of the Src family in the CA1 region of the hippocampus.
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Hippocampal NMDA receptors and subsequent signaling pathways are involved in the mechanism for extinction of contextual fear.
“In addition to amygdaloid NMDA receptors, emerging evidence has recently indicated that hippocampal NMDA receptors (NMDARs) and subsequent signaling pathways are involved in the mechanism for extinction of contextual fear (Bevilaqua et al, 2005;Szapiro et al, 2003).”
From Effects of Single Prolonged Stress and D-Cycloserine on Contextual Fear Extinction and Hippocampal NMDA Receptor Expression in a Rat Model of PTSD (2008) · cites this paper as Bevilaqua et al, 2005
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Neural Mechanisms of Extinction Learning and Retrieval
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- Authors
- BEVILAQUA, L., DASILVA, W., MEDINA, J., IZQUIERDO, I., & CAMMAROTA, M.
- Affiliations
- Universidade Federal do Rio Grande do Sul (BR)
- Corresponding author
- CAMMAROTA, M
- Venue
- Pharmacology Biochemistry and Behavior
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 81
- Issue
- 1
- Pages
- 139-145
- ISSN
- 0091-3057 (ISSN-L)
- OpenAlex
- W2063140187
- Cited by
- 35
- References
- 68
- Citations by year
- 2023: 1 · 2022: 1 · 2019: 1 · 2018: 2 · 2016: 1 · 2015: 4 · 2014: 1 · 2013: 3
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacology Biochemistry and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Consejo Nacional de Investigaciones Científicas y Técnicas
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Agencia Nacional de Promoción Científica y Tecnológica
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- fear extinction, Src family kinases, hippocampal CA1, passive avoidance, PP2, long-term potentiation, memory consolidation, avoidance response
- MeSH terms
- Animals, Extinction, Psychological, Fear, Hippocampus, Male, Memory, Pyrimidines, Reaction Time, Rats, Wistar, src-Family Kinases, Rats
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