Activation of EphB2 Forward Signaling Enhances Memory Consolidation

Alapin, Jessica M.; Dines, Monica; Vassiliev, Maria; Tamir, Tal; Ram, Alon; Locke, Clifford; Ji, Yu; Lamprecht, Raphael

doi:10.1016/j.celrep.2018.04.042

Cited by 27 publications

(26 citation statements)

References 40 publications

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“…We demonstrated that EphB2 played an important role in SI-induced memory forgetting, which strengthens the evidence that EphB2 is involved in enhancing synaptic transmission, and the gene expression is believed to underlie memory formation 39,41,54,55 . EphB2 interacts with NMDA receptors and regulates excitatory synapse formation.…”

Section: Discussionsupporting

confidence: 83%

“…Together with the accumulating evidences, EphB2 mediates the excitatory synaptogenesis during development and coordinates synaptic plasticity by controlling the localization and function of glutamate receptors 27,59 . Previous studies also show that EphB2 signal is related to anxiety disorders 62 , autism 63,64 , and cognitive dysfunction 41,65 . Our study expands the understanding of the (see figure on previous page) Fig.…”

Section: Discussionmentioning

confidence: 78%

“…As EphB2 participates in memory regulation 39,41,42 , we hypothesized that the downregulation of EphB2 could mimic the behavioral abnormalities in SI mice. We thus generated a lentiviral vector expressing both green fluorescent protein (GFP) and EphB2 shRNA (Lenti-sh-EphB2) (referred to as "EphB2-shRNA") 14 to knock down EphB2 ( Supplementary Figs.…”

Section: Ephb2 Mediates the Social Isolation-induced Memory Forgettingmentioning

confidence: 99%

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EphB2 mediates social isolation-induced memory forgetting

et al. 2020

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Social isolation in adolescence leads to lasting deficits, including emotional and cognitive dysregulation. It remains unclear, however, how social isolation affects certain processes of memory and what molecular mechanisms are involved. In this study, we found that social isolation during the post-weaning period resulted in forgetting of the long-term fear memory, which was attributable to the downregulation of synaptic function in the hippocampal CA1 region mediated by EphB2, a receptor tyrosine kinase which involves in the glutamate receptor multiprotein complex. Viral-mediated EphB2 knockdown in CA1 mimicked the memory defects in group-housed mice, whereas restoration of EphB2 by either viral overexpression or resocialization reversed the memory decline in isolated mice. Taken together, our finding indicates that social isolation gives rise to memory forgetting by disrupting EphB2-mediated synaptic plasticity, which may provide a potential target for preventing memory loss caused by social isolation or loneliness.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 78%

Section: Ephb2 Mediates the Social Isolation-induced Memory Forgettingmentioning

confidence: 99%

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EphB2 mediates social isolation-induced memory forgetting

et al. 2020

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“…Indeed, EphB2 loss was shown to attenuate LTP (Grunwald et al, 2001;Henderson et al, 2001) and to impair LTD (Grunwald et al, 2001). While the loss of EphB2 function impairs long-term memory formation, photo-activation of EphB2 using optogenetics during fear conditioning learning enhances long-term memory (Alapin et al, 2018). However, our previous study showed no effects of astrocytic ephrin-B1 deletion on LTP induction and consolidation in the adult hippocampus of naïve WT and KO mice (Koeppen et al, 2018).…”

Section: Discussionmentioning

confidence: 91%

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

Nguyen

Koeppen

Woodruff

et al. 2020

Front. Synaptic Neurosci.

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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.

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“…In a separate cohort of mice, after bilateral stereotactic injection of AAV constructs at both regions, guide steel cannulas (23gauge) were inserted 1 mm above the aIC, to allow local delivery of CNO upon recovery. Cannula placement was secured using dental cement as previously described (Alapin et al, 2018). After viral delivery and appropriate cleaning and suturing (Vetbond) of the exposed skull, animals were administered an additional intraperitoneal dose of 0.5 mg/kg Norocarp, as well as 0.5 mg/kg Baytril (enrofloxacin).…”

Section: Surgery and Viral Injectionmentioning

confidence: 99%

Activity of Insula to Basolateral Amygdala Projecting Neurons is Necessary and Sufficient for Taste Valence Representation

Kayyal¹,

Yiannakas²,

Chandran³

et al. 2019

J. Neurosci.

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Conditioned taste aversion (CTA) is an associative learning paradigm, wherein consumption of an appetitive tastant (e.g., saccharin) is paired to the administration of a malaise-inducing agent, such as intraperitoneal injection of LiCl. Aversive taste learning and retrieval require neuronal activity within the anterior insula (aIC) and the basolateral amygdala (BLA). Here, we labeled neurons of the aIC projecting to the BLA in adult male mice using a retro-AAV construct and assessed their necessity in aversive and appetitive taste learning. By restricting the expression of chemogenetic receptors in aIC-to-BLA neurons, we demonstrate that activity within the aICto-BLA projection is necessary for both aversive taste memory acquisition and retrieval, but not for its maintenance, nor its extinction. Moreover, inhibition of the projection did not affect incidental taste learning per se, but effectively suppressed aversive taste memory retrieval when applied either during or before the encoding of the unconditioned stimulus for CTA (i.e., malaise). Remarkably, activation of the projection after novel taste consumption, without experiencing any internal discomfort, was sufficient to form an artificial aversive taste memory, resulting in strong aversive behavior upon retrieval. Our results indicate that aIC-to-BLA projecting neurons are an essential component in the ability of the brain to associate taste sensory stimuli with body states of negative valence and guide the expression of valence-specific behavior upon taste memory retrieval.

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Activation of EphB2 Forward Signaling Enhances Memory Consolidation

Cited by 27 publications

References 40 publications

EphB2 mediates social isolation-induced memory forgetting

EphB2 mediates social isolation-induced memory forgetting

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

Activity of Insula to Basolateral Amygdala Projecting Neurons is Necessary and Sufficient for Taste Valence Representation

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