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Endothelin-1-induced mini-stroke in the dorsal hippocampus or lateral amygdala results in deficits in learning and memory.

Sheng T, Zhang X, Wang S, Zhang J, Lu W, Dai Y - J Biomed Res (2015)

Bottom Line: In novel object task, ET-1 in the hippocampus also eliminated object identity memory.ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear, but did not impair retention of contextual fear.These findings suggest that ET-1-induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions.

View Article: PubMed Central - PubMed

Affiliation: The Center of Metabolic Disease Research.

ABSTRACT
Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is still unknown. Here, we first established a mini-stroke model by infusion of endothelin-1 (ET-1) into the dorsal hippocampus or the lateral amygdala, and then investigated how these mini-infarcts affected brain functions associated with these regions. We found that rats with ET-1 infusion showed deficit in recall of contextual fear memory, but not in learning process and recall of tone fear memory. In novel object task, ET-1 in the hippocampus also eliminated object identity memory. ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear, but did not impair retention of contextual fear. These findings suggest that ET-1-induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions.

No MeSH data available.


Related in: MedlinePlus

ET-1 induced mini-stroke in the dorsal hippocampal (DH) region impairs recall of contextual fear memory.A: Schematic of fear conditioning protocol. B: Rats with ET-1-induced dorsal hippocampal mini-stroke exhibit normal freezing percentage in a 6-trial training protocol. ITI: inter train interval. C: Freezing during 3 minutes of testing in the training context (*P<0.05, two-tailed Student's t-test) but not in a novel context (P=0.470, two-tailed Student's t-test) is significantly impaired in ET-1 infused rats (sham, n=9, DH-stroke, n=9). D: Tone conditioning is unaffected in ET-1 injected rats 2 hours after training (no significant main effect of treatment, F(1, 42)=1.991, P=0.878).
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f02: ET-1 induced mini-stroke in the dorsal hippocampal (DH) region impairs recall of contextual fear memory.A: Schematic of fear conditioning protocol. B: Rats with ET-1-induced dorsal hippocampal mini-stroke exhibit normal freezing percentage in a 6-trial training protocol. ITI: inter train interval. C: Freezing during 3 minutes of testing in the training context (*P<0.05, two-tailed Student's t-test) but not in a novel context (P=0.470, two-tailed Student's t-test) is significantly impaired in ET-1 infused rats (sham, n=9, DH-stroke, n=9). D: Tone conditioning is unaffected in ET-1 injected rats 2 hours after training (no significant main effect of treatment, F(1, 42)=1.991, P=0.878).

Mentions: We investigated the acquisition of the association memory between fear and tone. We trained adult male rats (sham and DH-stroke treatment) using a tone fear conditioning protocol (Fig. 2A). Intact hippocampal function is critical for eliciting contextual fear conditioning (freezing in response to training context exposure), but not for tone (freezing in response to tone presentation) fear conditioning in response to this training protocol[24,30-31]. In contrast, rats with ET-1 induced mini-stroke in the dorsal hippocampus rats learned fear memory as well as controls did (Fig. 2B). When tested 2 hours after training, dorsal hippocampus-stroke resulted in a dramatic reduction in retention of contextual fear memory (Fig. 2C) and normal tone fear memory (Fig. 2D). These data provide evidence that ET-1 in the dorsal hippocampus induced hippocampal lesion and impaired hippocampus-dependent fear learning in adult rats.


Endothelin-1-induced mini-stroke in the dorsal hippocampus or lateral amygdala results in deficits in learning and memory.

Sheng T, Zhang X, Wang S, Zhang J, Lu W, Dai Y - J Biomed Res (2015)

ET-1 induced mini-stroke in the dorsal hippocampal (DH) region impairs recall of contextual fear memory.A: Schematic of fear conditioning protocol. B: Rats with ET-1-induced dorsal hippocampal mini-stroke exhibit normal freezing percentage in a 6-trial training protocol. ITI: inter train interval. C: Freezing during 3 minutes of testing in the training context (*P<0.05, two-tailed Student's t-test) but not in a novel context (P=0.470, two-tailed Student's t-test) is significantly impaired in ET-1 infused rats (sham, n=9, DH-stroke, n=9). D: Tone conditioning is unaffected in ET-1 injected rats 2 hours after training (no significant main effect of treatment, F(1, 42)=1.991, P=0.878).
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Related In: Results  -  Collection

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f02: ET-1 induced mini-stroke in the dorsal hippocampal (DH) region impairs recall of contextual fear memory.A: Schematic of fear conditioning protocol. B: Rats with ET-1-induced dorsal hippocampal mini-stroke exhibit normal freezing percentage in a 6-trial training protocol. ITI: inter train interval. C: Freezing during 3 minutes of testing in the training context (*P<0.05, two-tailed Student's t-test) but not in a novel context (P=0.470, two-tailed Student's t-test) is significantly impaired in ET-1 infused rats (sham, n=9, DH-stroke, n=9). D: Tone conditioning is unaffected in ET-1 injected rats 2 hours after training (no significant main effect of treatment, F(1, 42)=1.991, P=0.878).
Mentions: We investigated the acquisition of the association memory between fear and tone. We trained adult male rats (sham and DH-stroke treatment) using a tone fear conditioning protocol (Fig. 2A). Intact hippocampal function is critical for eliciting contextual fear conditioning (freezing in response to training context exposure), but not for tone (freezing in response to tone presentation) fear conditioning in response to this training protocol[24,30-31]. In contrast, rats with ET-1 induced mini-stroke in the dorsal hippocampus rats learned fear memory as well as controls did (Fig. 2B). When tested 2 hours after training, dorsal hippocampus-stroke resulted in a dramatic reduction in retention of contextual fear memory (Fig. 2C) and normal tone fear memory (Fig. 2D). These data provide evidence that ET-1 in the dorsal hippocampus induced hippocampal lesion and impaired hippocampus-dependent fear learning in adult rats.

Bottom Line: In novel object task, ET-1 in the hippocampus also eliminated object identity memory.ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear, but did not impair retention of contextual fear.These findings suggest that ET-1-induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions.

View Article: PubMed Central - PubMed

Affiliation: The Center of Metabolic Disease Research.

ABSTRACT
Functional and structural alterations in brain connectivity associated with brain ischemia have been extensively studied. However, the mechanism whereby local ischemia in deep brain region affect brain functions is still unknown. Here, we first established a mini-stroke model by infusion of endothelin-1 (ET-1) into the dorsal hippocampus or the lateral amygdala, and then investigated how these mini-infarcts affected brain functions associated with these regions. We found that rats with ET-1 infusion showed deficit in recall of contextual fear memory, but not in learning process and recall of tone fear memory. In novel object task, ET-1 in the hippocampus also eliminated object identity memory. ET-1 in the lateral amygdale affected acquisition of fear conditioning and disrupted retention of tone-conditioned fear, but did not impair retention of contextual fear. These findings suggest that ET-1-induced mini-infarct in deep brain area leads to functional deficits in learning and memory associated with these regions.

No MeSH data available.


Related in: MedlinePlus