Endothelin-1-induced mini-stroke in the dorsal hippocampus or lateral amygdala results in deficits in learning and memory.
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.
Affiliation: The Center of Metabolic Disease Research.
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.
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Mentions: We further studied whether and how ET-1 induced mini-stroke in the lateral amygdala would affect brain functions associated with this subcortical region. Twenty-four hours after ET-1 injection, we used T2-weighted MRI to examine the region of ischemia (Fig. 4A and B). Rats with bilateral lateral amygdala mini-stroke showed normal exercise capacity (Fig. 4C-4F) as the precondition of the following test. The lateral amygdala is imperative for obtaining the association of cued message and emotional memory, and is also critical for tone fear conditioning, but not for contextual fear memory[23-24]. We trained rats of both groups using the protocol as shown in Fig. 2A. Compared to sham rats, lateral amygdala-stroke mice learned the association between shock and tone/context more tardily indicated by a delayed increase in freezing percentage during 6 training trials (Fig. 5A). Two hours later, rats were positioned in training context, neither sham nor lateral amygdala-stroke rats showed significant freezing behavior in the training context (Fig. 5B). Then, rats were placed in a novel context and presented with only the tone. Lateral amygdala -stroke rats showed a dramatic reduction in retention of ton fear memory (Fig. 5C). These results indicated that rats with bilateral lateral amygdala mini-stroke show deficits in tone components of aversive conditioning with contextual fear memory kept intact.
No MeSH data available.