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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 infusion in the dorsal hippocampus impairs recognition memory.A: Schematic of novel object recognition task. B: Color-coded time-in-location map in the training session. The same objects were positioned bottom-left and upper-right. C: The amount of time spent in exploring the two objects was the same for treatments. Dotted line represents performance at chance (50%). (D) Color-coded map and (E) discrimination ratio in testing session show the impairment of object discriminate memory in the ET-1 infused rats (sham, n=9, DH-stroke, n=9, *P<0.05, two-tailed Student's t-test). The same blue-to-red scale is used for each map. DH: dorsal hippocampus.
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f03: ET-1 infusion in the dorsal hippocampus impairs recognition memory.A: Schematic of novel object recognition task. B: Color-coded time-in-location map in the training session. The same objects were positioned bottom-left and upper-right. C: The amount of time spent in exploring the two objects was the same for treatments. Dotted line represents performance at chance (50%). (D) Color-coded map and (E) discrimination ratio in testing session show the impairment of object discriminate memory in the ET-1 infused rats (sham, n=9, DH-stroke, n=9, *P<0.05, two-tailed Student's t-test). The same blue-to-red scale is used for each map. DH: dorsal hippocampus.

Mentions: Then, we used the novel-object-recognition task (Fig. 3A) to assess recognition memory, which also requires the hippocampus[32-33], in ET-1-infused animals. During training session, 2 treatments had no significant difference in time that rats spent in exploring the 2 novel objects (as shown by hot map and exploratory preference; Fig. 3B and 3C), indicating that both groups of rats had the same motivation and curiosity to explore the objects. During the testing stage, one of the familiar objects used in the training was replaced by a novel object, and rats were allowed to explore for 5 minutes. At the 2-hour retention test, rats of the ET-1 infusion dorsal hippocampus-stroke groups showed dramatic reduction in time exploring the novel objects compared to the sham group, indicated by the color-coded map (Fig. 3D). In contrast, preference towards the familiar object was similar between the 2 groups (as shown by the discrimination ratio, Fig. 3E). This indicated that ET-1 in the dorsal hippocampus impaired capability of rats to identify and recognize novel objects.


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 infusion in the dorsal hippocampus impairs recognition memory.A: Schematic of novel object recognition task. B: Color-coded time-in-location map in the training session. The same objects were positioned bottom-left and upper-right. C: The amount of time spent in exploring the two objects was the same for treatments. Dotted line represents performance at chance (50%). (D) Color-coded map and (E) discrimination ratio in testing session show the impairment of object discriminate memory in the ET-1 infused rats (sham, n=9, DH-stroke, n=9, *P<0.05, two-tailed Student's t-test). The same blue-to-red scale is used for each map. DH: dorsal hippocampus.
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Related In: Results  -  Collection

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f03: ET-1 infusion in the dorsal hippocampus impairs recognition memory.A: Schematic of novel object recognition task. B: Color-coded time-in-location map in the training session. The same objects were positioned bottom-left and upper-right. C: The amount of time spent in exploring the two objects was the same for treatments. Dotted line represents performance at chance (50%). (D) Color-coded map and (E) discrimination ratio in testing session show the impairment of object discriminate memory in the ET-1 infused rats (sham, n=9, DH-stroke, n=9, *P<0.05, two-tailed Student's t-test). The same blue-to-red scale is used for each map. DH: dorsal hippocampus.
Mentions: Then, we used the novel-object-recognition task (Fig. 3A) to assess recognition memory, which also requires the hippocampus[32-33], in ET-1-infused animals. During training session, 2 treatments had no significant difference in time that rats spent in exploring the 2 novel objects (as shown by hot map and exploratory preference; Fig. 3B and 3C), indicating that both groups of rats had the same motivation and curiosity to explore the objects. During the testing stage, one of the familiar objects used in the training was replaced by a novel object, and rats were allowed to explore for 5 minutes. At the 2-hour retention test, rats of the ET-1 infusion dorsal hippocampus-stroke groups showed dramatic reduction in time exploring the novel objects compared to the sham group, indicated by the color-coded map (Fig. 3D). In contrast, preference towards the familiar object was similar between the 2 groups (as shown by the discrimination ratio, Fig. 3E). This indicated that ET-1 in the dorsal hippocampus impaired capability of rats to identify and recognize novel objects.

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