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A reexamination of the role of the hippocampus in object-recognition memory using neurotoxic lesions and ischemia in rats

Paradoxical results on object-recognition delayed nonmatching-to-sample (DNMS)
tasks have been found in monkeys and rats that receive either partial, ischemia-induced
hippocampal lesions or complete hippocampal ablation. Ischemia results in severe DNMS
impairments, which have been attributed to circumscribed CA1 cell loss. However,
ablation studies indicate that the hippocampus plays only a minimal role in the performance
of the DNMS task. Two hypotheses have been proposed to account for these discrepant
findings (Bachevalier & Mishkin, 1989). First, the "hippocampal interference" hypothesis
posits that following ischemia, the partially damaged hippocampus may disrupt activity in
extrahippocampal structures that are important for object-recognition memory. Second,
previously undetected ischemia-induced extrahippocampal damage may be responsible for
the DNMS impairments attributed to CA1 cell loss.
To test the "hippocampal interference" hypothesis, the effect of partial NMDAinduced
lesions of the dorsal hippocampus were investigated on DNMS performance in
rats. These lesions damaged much of the same area, the CA1, as did ischemia; but did so
without depriving the entire forebrain of oxygen, thereby reducing the possibility of
extrahippocampal damage. In Experiment 1, rats were trained on the DNMS task prior to
receiving an NMDA-lesion. Postoperatively, these rats reacquired the nonmatching rule at
a rate equivalent to controls and were unimpaired in performance at delays up to 300 s. In
Experiment 2, naive rats were given NMDA-lesions and then trained on DNMS. These
rats acquired the DNMS rule at a rate equivalent to controls and performed normally at
delays up to 300 s. These findings suggest that interference from a partially damaged
hippocampus cannot account for the ischemia-induced DNMS impairments and that they
are more likely produced by extrahippocampal neuropathology. In Experiment 3, rats from
the previous study were tested on the Morris water-maze. Compared to sham-lesioned
animals, rats with partial lesions of the dorsal hippocampus were impaired in the
acquisition of the water-maze task. Thus, subtotal NMDA-lesions of the hippocampus
impaired spatial memory while leaving nonspatial memory intact.
Mumby et al. (1992b) suggested that the ischemia-induced extrahippocampal
damage underlying the DNMS deficits is mediated or produced by the postischemic
hippocampus. To test this idea, preoperatively trained rats in Experiment 4 were subject to
cerebral ischemia followed within 1hr by hippocampal aspiration lesions. It was
hypothesized that ablation soon after ischemia would block the damage putatively produced
by the postischemic hippocampus and thereby prevent the development of postoperative
DNMS deficits. Unlike "ischemia-only" rats, the rats with the combined lesion were able to
reacquire the nonmatching rule at a normal rate and performed normally at delays up to 300
s. Thus, hippocampectomy soon after ischemia eliminated the pathogenic process that lead
to ischemia-induced DNMS deficits. Experiment 5 investigated the role of ischemiainduced
CA1 cell death as a factor in the production of extrahippocampal neuropathology.
Naive rats were given NMDA-lesions of the dorsal hippocampus followed 3 weeks later by
cerebral ischemia. If the ischemia-induced CA1 neurotoxicity is responsible for producing
extrahippocampal damage then preischemic ablation should attenuate this process and
prevent the development of DNMS impairments. This did not occur: Rats with the
combined lesion were as impaired as the "ischemia-only" rats in the acquisition of the
DNMS task. This suggests that the ischemia-induced pathogenic processes that result in
extrahippocampal neuropathology comprise more than CA1 neurotoxicity.
The findings presented in this thesis are consistent with the idea that ischemiainduced
DNMS deficits in rats are the result of extrahippocampal damage mediated or
produced by the postischemic hippocampus. The discussion focuses on three main points:
1) How might the post-ischemic hippocampus be involved in the production of
extrahippocampal neuropathology? 2) In what brain region(s) might this damage be
occurring? 3) What anatomical, molecular, or functional neuropathology might ischemia
produce in extrahippocampal brain regions? The results are also discussed in terms of a
specialized role for the hippocampus in mnemonic functions and the recently emphasized
importance of the rhinal cortex in object-recognition memory. / Arts, Faculty of / Psychology, Department of / Graduate
Date11 1900
CreatorsDuva, Christopher Adam
Source SetsUniversity of British Columbia
Detected LanguageEnglish
TypeText, Thesis/Dissertation
Format12243734 bytes, application/pdf
RightsFor non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use

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