The roles of Eph receptors in contextual fear conditioning memory formation

Dines, Monica; Grinberg, Svetlana; Vassiliev, Maria; Ram, Alon; Tamir, Tal; Lamprecht, Raphael

doi:10.1016/j.nlm.2015.07.003

Cited by 17 publications

(15 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A reduction of hippocampal EphB2 was associated with impaired cognitive function in a mouse model of Alzheimer's disease (Cisse et al, 2011;Simon et al, 2009), whereas EphB2 blockade in the amygdala hindered the development of restraint stress-induced anxiety (Attwood et al, 2011). EphB2 also has a role in emotional learning and memory (Cruz et al, 2015;Dines et al, 2015;Trabalza et al, 2012). In the present study, we found that EphB2 activation in the mPFC promoted resilience to stress, whereas EphB2 knockdown in the mPFC induced depressive-like behaviors in the subthreshold social defeat stress paradigm.…”

Section: Discussionmentioning

confidence: 99%

EphB2 in the Medial Prefrontal Cortex Regulates Vulnerability to Stress

Zhang

Han

Chen

et al. 2016

Neuropsychopharmacol

View full text Add to dashboard Cite

The ephrin B2 (EphB2) receptor is a tyrosine kinase receptor that is associated with synaptic development and maturation. It has recently been implicated in cognitive deficits and anxiety. However, still unknown is the involvement of EphB2 in the vulnerability to stress. In the present study, we observed decreases in EphB2 levels and their downstream molecules in the medial prefrontal cortex (mPFC) but not in the orbitofrontal cortex (OFC) in mice that were susceptible to chronic social defeat stress. The activation of EphB2 receptors with EphrinB1-Fc in the mPFC produced stress-resistant and antidepressant-like behavioral effects in susceptible mice that lasted for at least 10 days. EphB2 receptor knockdown by short-hairpin RNA in the mPFC increased the susceptibility to stress and induced depressive-like behaviors in a subthreshold chronic social defeat stress paradigm. These behavioral effects were associated with changes in the phosphorylation of cofilin and membrane α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking and the expression of some synaptic proteins in the mPFC. We also found that EphB2 regulated stress-induced spine remodeling in the mPFC. Altogether, these results indicate that EphB2 is a critical regulator of stress vulnerability and might be a potential target for the treatment of depression.

show abstract

Section: Discussionmentioning

confidence: 99%

EphB2 in the Medial Prefrontal Cortex Regulates Vulnerability to Stress

Zhang

Han

Chen

et al. 2016

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Furthermore, pathway analysis revealed several nervous system related pathways significantly associated with memory performance. Among them, glioma, mTOR signaling pathway, axon guidance, and Ephrin receptor signaling have been related with memory functions in previous literature [39][40][41][42]; it is of note that mTOR signaling in hippocampus is necessary for memory formation [40], while other associated pathways are somewhat linked with mTOR signaling pathway, which further supports the involvement of these pathways in memory functions.…”

Section: Discussionmentioning

confidence: 54%

Multi-level genomic analyses suggest new genetic variants involved in human memory

et al. 2018

View full text Add to dashboard Cite

Development of high-throughput genotyping platforms provides an opportunity to identify new genetic elements related to complex cognitive functions. Taking advantage of multi-level genomic analysis, here we studied the genetic basis of human short-term (STM, n = 1623) and long-term (LTM, n = 1522) memory functions. Heritability estimation based on single nucleotide polymorphism showed moderate (61%, standard error 35%) heritability of short-term memory but almost zero heritability of long-term memory. We further performed a two-step genome-wide association study, but failed to find any SNPs that could pass genome-wide significance and survive replication at the same time. However, suggestive significance for rs7011450 was found in the shared component of the two STM tasks. Further inspections on its nearby gene zinc finger and at-hook domain containing and SNPs around this gene showed suggestive association with STM. In LTM, a polymorphism within branched chain amino acid transaminase 2 showed suggestive significance in the discovery cohort and has been replicated in another independent population of 1862. Furthermore, we performed a pathway analysis based on the current genomic data and found pathways including mTOR signaling and axon guidance significantly associated with STM capacity. These findings warrant further replication in other larger populations.

show abstract

“…Furthermore, the loss of EphA4 and EphB2 receptors are reported to affect associative memory in mice (Gerlai et al, 1999;Halladay et al, 2004;Willi et al, 2012;Dines et al, 2015). Interestingly, EphB2 loss affects both short and long-term contextual fear conditioning memory formation, but only long-term memory depends on EphB2 forward signaling (Dines et al, 2015). Disruption of ephrin-B reverse signaling in neurons was also implicated in impaired hippocampal-dependent learning and memory in EphB2 KO mice (Grunwald et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…Trans-synaptic Eph/ephrin-B interactions promote postsynaptic dendritic spine formation and maturation during development (Henderson et al, 2001;Henkemeyer et al, 2003;Kayser et al, 2006) and high levels of EphB receptors and ephrins are retained in the adult hippocampus (Grunwald et al, 2001;Liebl et al, 2003). Furthermore, the loss of EphA4 and EphB2 receptors are reported to affect associative memory in mice (Gerlai et al, 1999;Halladay et al, 2004;Willi et al, 2012;Dines et al, 2015). Interestingly, EphB2 loss affects both short and long-term contextual fear conditioning memory formation, but only long-term memory depends on EphB2 forward signaling (Dines et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Astrocytic Ephrin-B1 Controls Synapse Formation in the Hippocampus During Learning and Memory

Nguyen

Koeppen

Woodruff

et al. 2020

Front. Synaptic Neurosci.

View full text Add to dashboard Cite

Astrocytes play a fundamental role in synapse formation, pruning, and plasticity, which are associated with learning and memory. However, the role of astrocytes in learning and memory is still largely unknown. Our previous study showed that astrocytespecific ephrin-B1 knockout (KO) enhanced but ephrin-B1 overexpression (OE) in hippocampal astrocytes impaired contextual memory recall following fear conditioning. The goal of this study was to understand the mechanism by which astrocytic ephrin-B1 influences learning; specifically, learning-induced remodeling of synapses and dendritic spines in CA1 hippocampus using fear-conditioning paradigm. While we found a higher dendritic spine density and clustering on c-Fos-positive (+) neurons activated during contextual memory recall in both wild-type (WT) and KO mice, overall spine density and mEPSC amplitude were increased in CA1 neurons of KO compared to WT. In contrast, ephrin-B1 OE in hippocampal astrocytes impaired dendritic spine formation and clustering, specifically on c-Fos(+) neurons, coinciding with an overall decrease in vGlut1/PSD95 co-localization. Although astrocytic ephrin-B1 influenced learninginduced spine formation, the changes in astrocytic ephrin-B1 levels did not affect spine enlargement as no genotype differences in spine volume were observed between trained WT, KO, and OE groups. Our results suggest that a reduced formation of new spines rather than spine maturation in activated CA1 hippocampal neurons is most likely responsible for impaired contextual learning in OE mice due to abundantly high ephrin-B1 levels in astrocytes. The ability of astrocytic ephrin-B1 to negatively influence new spine formation during learning can potentially regulate new synapse formation at specific dendritic domains and underlie memory encoding.

show abstract

The roles of Eph receptors in contextual fear conditioning memory formation

Cited by 17 publications

References 36 publications

EphB2 in the Medial Prefrontal Cortex Regulates Vulnerability to Stress

EphB2 in the Medial Prefrontal Cortex Regulates Vulnerability to Stress

Multi-level genomic analyses suggest new genetic variants involved in human memory

Astrocytic Ephrin-B1 Controls Synapse Formation in the Hippocampus During Learning and Memory

Contact Info

Product

Resources

About