Comparison of the amnesic deficits associated with damage to the medial temporal lobe, medial diencephalon, or basal forebrain in rats
Creators: name: Kornecook, Tom John
Publisher: name: University of British Columbia
Year: 2009

description: There is general agreement that human brain-damaged-produced amnesia can be caused by damage in one of three separate brain regions: (1) the medial temporal lobe, (2) the medial diencephalon, or (3) the basal forebrain. However, the issue of whether there is a unitary amnesic syndrome, or whether the amnesia produced by damage to these three different brain areas are qualitatively distinct remains a matter of debate. The major purpose of the experiments in this thesis was to compare the nature of the impairment in memory for objects associated with bilateral medial-temporal-lobe, medial-diencephalic, or basal-forebrain damage in rats. Four experiments comprise this thesis. Experiments 1, 2, and 3 described the effects of selective damage to the medial temporal lobe, basal forebrain, or medial diencephalon on a battery of anterograde object-memory tasks. This test battery included: (i) object discrimination, (ii) discrimination reversal, (iii) eight-pair concurrent object discrimination, (iv) delayed nonmatching-to-sample (DNMS) with retention delays of 4, 15, 30, 60, and 120 s, (v) DNMS with lists of three, five , and seven sample objects, and (vi) order discrimination. In Experiment 1, rats with lesions of the hippocampus were impaired only in the acquisition of the simple and concurrent object-discrimination tasks, whereas rats with lesions of the amygdala were impaired only in the acquisition of the concurrent-object-discrimination and DNMS tasks. Both groups were able to learn all tasks to the same level as controls, and once the tasks were learned, they did not display any impairments when the mnemonic demands of the task were increased. In Experiment 2, rats with lesions of either the rhinal cortex or basal forebrain (i.e., medial septum and diagonal band) displayed DNMS deficits at all retention delays longer than 4 s and all sample list lengths, and they were impaired on the order-discrimination task. Rhinal-lesioned rats were also impaired in learning the object-discrimination, discrimination-reversal, and concurrent-object-discrimination tasks, but not the DNMS task, whereas basal-forebrain-lesioned rats displayed the exact opposite pattern of deficits on these four tasks. In Experiment 3, lesions of the mediodorsal thalamus in rats produced a profile of anterograde object-memory deficits similar to that produced by lesions of the rhinal cortex in Experiment 2. However, thalamiclesioned rats also displayed evidence of an abnormal perseverative tendency on the discrimination-reversal task and, unlike the delay-dependent DNMS deficit seen in the rhinallesioned rats, their DNMS impairment was delay-independent. Experiment 4 was an analysis of the retrograde object-memory impairment associated with damage to the medial temporal lobe, medial diencephalon, or basal forebrain. Rats with lesions of the rhinal cortex or basal forebrain (i.e., medial septum and diagonal band) were impaired relative to controls in the retention of object-discrimination problems learned 2 or 9 days, but 16, 37, or 58 days, prior to surgery; in contrast, lesions of the mediodorsal thalamus had no significant effect. The present experiments demonstrated that lesions of the medial temporal lobe, medial diencephalon, or basal forebrain in rats produce different profiles of anterograde and retrograde object-memory deficits, thereby establishing that different syndromes of amnesia result from damage to the various memory structures of the brain. The scope and systematic nature of the present experiments are without parallel in this field of research. Their findings confirm and extend the results of less comprehensive human clinical studies and monkey and rat experiments. In doing so, they underscore the value of the comparative approach in the study of the neuroanatomy of brain-damage-produced amnesia.