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EphrinA4 mimetic peptide targeted to EphA binding site impairs the formation of long-term fear memory in lateral amygdala.

Dines M, Lamprecht R - Transl Psychiatry (2014)

Bottom Line: Acute systemic administration of pep-ephrinA4 1 h after training also impaired long-term fear conditioning memory formation.These results demonstrate that ephrinA4 binding sites in LA are essential for long-term fear memory formation.Moreover, our research shows that ephrinA4 binding sites may serve as a target for pharmacological treatment of fear and anxiety disorders.

View Article: PubMed Central - PubMed

Affiliation: Sagol Department of Neurobiology, University of Haifa, Haifa, Israel.

ABSTRACT
Fear conditioning leads to long-term fear memory formation and is a model for studying fear-related psychopathologies conditions such as phobias and posttraumatic stress disorder. Long-term fear memory formation is believed to involve alterations of synaptic efficacy mediated by changes in synaptic transmission and morphology in lateral amygdala (LA). EphrinA4 and its cognate Eph receptors are intimately involved in regulating neuronal morphogenesis, synaptic transmission and plasticity. To assess possible roles of ephrinA4 in fear memory formation we designed and used a specific inhibitory ephrinA4 mimetic peptide (pep-ephrinA4) targeted to EphA binding site. We show that this peptide, composed of the ephrinA4 binding domain, interacts with EphA4 and inhibits ephrinA4-induced phosphorylation of EphA4. Microinjection of the pep-ephrinA4 into rat LA 30 min before training impaired long- but not short-term fear conditioning memory. Microinjection of a control peptide derived from a nonbinding E helix site of ephrinA4, that does not interact with EphA, had no effect on fear memory formation. Microinjection of pep-ephrinA4 into areas adjacent to the amygdala had no effect on fear memory. Acute systemic administration of pep-ephrinA4 1 h after training also impaired long-term fear conditioning memory formation. These results demonstrate that ephrinA4 binding sites in LA are essential for long-term fear memory formation. Moreover, our research shows that ephrinA4 binding sites may serve as a target for pharmacological treatment of fear and anxiety disorders.

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Related in: MedlinePlus

Acute systemic administration of ephrinA4 mimetic peptide impairs long-term fear conditioning memory (LTM) formation. Pep-ephrinA4 (0.2 mg; n=15), or saline (n=14) was injected subcutaneously 1 h after fear conditioning. Long-term memory was tested 24 h after training. Animals injected with pep-ephrinA4 were significantly impaired in fear memory (F(1)=8.6, P<0.008) when compared with saline-injected rats. CS, conditioned stimulus.
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fig4: Acute systemic administration of ephrinA4 mimetic peptide impairs long-term fear conditioning memory (LTM) formation. Pep-ephrinA4 (0.2 mg; n=15), or saline (n=14) was injected subcutaneously 1 h after fear conditioning. Long-term memory was tested 24 h after training. Animals injected with pep-ephrinA4 were significantly impaired in fear memory (F(1)=8.6, P<0.008) when compared with saline-injected rats. CS, conditioned stimulus.

Mentions: The aforementioned results show that ephrinA4 binding sites may serve as a target for pharmacological treatment of fear-related disorders. Application of drugs is most useful after trauma and systemically. We therefore tested the effects of pep-ephrinA4 injected subcutaneously 1 h after fear conditioning training. As shown in Figure 4, freezing during long-term memory test in animals injected with the pep-ephrinA4 (n=15) was significantly lower than animals injected with saline (n=14; F(1)=8.6, P<0.008). The treatment × tone trial interaction was not significant (F(4)=0.939, P>0.4). These results show that systemic administration of the pep-ephrinA4 impairs fear memory formation.


EphrinA4 mimetic peptide targeted to EphA binding site impairs the formation of long-term fear memory in lateral amygdala.

Dines M, Lamprecht R - Transl Psychiatry (2014)

Acute systemic administration of ephrinA4 mimetic peptide impairs long-term fear conditioning memory (LTM) formation. Pep-ephrinA4 (0.2 mg; n=15), or saline (n=14) was injected subcutaneously 1 h after fear conditioning. Long-term memory was tested 24 h after training. Animals injected with pep-ephrinA4 were significantly impaired in fear memory (F(1)=8.6, P<0.008) when compared with saline-injected rats. CS, conditioned stimulus.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4203006&req=5

fig4: Acute systemic administration of ephrinA4 mimetic peptide impairs long-term fear conditioning memory (LTM) formation. Pep-ephrinA4 (0.2 mg; n=15), or saline (n=14) was injected subcutaneously 1 h after fear conditioning. Long-term memory was tested 24 h after training. Animals injected with pep-ephrinA4 were significantly impaired in fear memory (F(1)=8.6, P<0.008) when compared with saline-injected rats. CS, conditioned stimulus.
Mentions: The aforementioned results show that ephrinA4 binding sites may serve as a target for pharmacological treatment of fear-related disorders. Application of drugs is most useful after trauma and systemically. We therefore tested the effects of pep-ephrinA4 injected subcutaneously 1 h after fear conditioning training. As shown in Figure 4, freezing during long-term memory test in animals injected with the pep-ephrinA4 (n=15) was significantly lower than animals injected with saline (n=14; F(1)=8.6, P<0.008). The treatment × tone trial interaction was not significant (F(4)=0.939, P>0.4). These results show that systemic administration of the pep-ephrinA4 impairs fear memory formation.

Bottom Line: Acute systemic administration of pep-ephrinA4 1 h after training also impaired long-term fear conditioning memory formation.These results demonstrate that ephrinA4 binding sites in LA are essential for long-term fear memory formation.Moreover, our research shows that ephrinA4 binding sites may serve as a target for pharmacological treatment of fear and anxiety disorders.

View Article: PubMed Central - PubMed

Affiliation: Sagol Department of Neurobiology, University of Haifa, Haifa, Israel.

ABSTRACT
Fear conditioning leads to long-term fear memory formation and is a model for studying fear-related psychopathologies conditions such as phobias and posttraumatic stress disorder. Long-term fear memory formation is believed to involve alterations of synaptic efficacy mediated by changes in synaptic transmission and morphology in lateral amygdala (LA). EphrinA4 and its cognate Eph receptors are intimately involved in regulating neuronal morphogenesis, synaptic transmission and plasticity. To assess possible roles of ephrinA4 in fear memory formation we designed and used a specific inhibitory ephrinA4 mimetic peptide (pep-ephrinA4) targeted to EphA binding site. We show that this peptide, composed of the ephrinA4 binding domain, interacts with EphA4 and inhibits ephrinA4-induced phosphorylation of EphA4. Microinjection of the pep-ephrinA4 into rat LA 30 min before training impaired long- but not short-term fear conditioning memory. Microinjection of a control peptide derived from a nonbinding E helix site of ephrinA4, that does not interact with EphA, had no effect on fear memory formation. Microinjection of pep-ephrinA4 into areas adjacent to the amygdala had no effect on fear memory. Acute systemic administration of pep-ephrinA4 1 h after training also impaired long-term fear conditioning memory formation. These results demonstrate that ephrinA4 binding sites in LA are essential for long-term fear memory formation. Moreover, our research shows that ephrinA4 binding sites may serve as a target for pharmacological treatment of fear and anxiety disorders.

Show MeSH
Related in: MedlinePlus