S. Rubio

Effects of mammillary body lesions on spatial reference and working memory tasks

This work examines the effects of electrolytic mammillary body (MB) lesions on the performance of rats in different spatial memory tasks in the Morris water maze. The first experiment assessed the effect of MB lesion on performance in a spatial reference memory task (place learning with multiple trials). The second experiment examined the effect of a lesion in this nucleus on performance in a spatial working memory task (single-trial place learning). The results show that lesion of the MB impairs the animals performance in spatial working memory tasks but does not impair acquisition in spatial reference memory tasks (place learning, transfer task, reversal task) or in a visual-cued task. However, the deficit in the spatial working memory task does not appear to vary with the delay between acquisition and retention trials (30 s and 5 min). Our results demonstrate a clear role of the mammillary bodies in the processing of spatial information in a working memory task. Lesion of the MB impairs performance in a working memory task but does not affect reference memory processes.

Effects of chronic alcohol consumption on spatial reference and working memory tasks.

The aim of this work was to determine the spatial memory impairments induced by chronic alcohol consumption in rats. The alcoholization process began on the 21st postnatal day and alcohol concentrations were gradually increased to reach a concentration of 20% that was maintained for 4 mon. Behavioral tests were performed in the Morris Water Maze (MWM). The first study assessed the effects of chronic alcohol intake on two reference memory tasks (a place learning with multiple trials and a new place learning carried out in the same experimental context). Alcohol-treated animals presented no overall impairment in their ability to process spatial information. Deficits were restricted to reduced behavioral flexibility in spatial strategies. The second study assessed working memory in two tasks in which information about platform location was only valid for one trial. In the first working memory task, the animals had to perform one trial per day and in the second task they were submitted to four trials per day. At the end of the second experiment, all animals were trained in a visual-cued task. In the second experiment, the most important deficits in alcohol-treated animals occur in spatial working memory tasks, and this impairment was independent of the intertrial interval used. In the second spatial working memory task, performance of the alcohol-treated animals in the earlier trials affected their performance in subsequent trials, suggesting that a process of proactive interference had taken place. The visual-cued task demonstrated that these behavioral impairments were produced without visuoperceptive impairments.

Effects of ageing on allocentric and egocentric spatial strategies in the Wistar rat

This study was designed to assess the effect of ageing on spatial (allocentric and egocentric) strategies in rats. Two different tasks were designed for this purpose: one involving Morris circular pool (distal extramaze cues) and another using the T water maze (egocentric cues). In the first task, the aged rats showed some difficulty in acquiring allocentric spatial learning skills. After increasing the number of trials in this task, there was no significant improvement in the performance of the aged group of rats compared to the adult group. However, in the second spatial task (using egocentric cues), both age groups gave a similar performance. Therefore, the effect of ageing on spatial learning depends on the strategy required to acquire this learning.

Improvement of spatial memory by (R)-α-methylhistamine, a histamine H3-receptor agonist, on the Morris water-maze in rat

This work aims to clarify the role of histamine in learning and memory. This is done by studying the effect of administration of the histamine precursor, L-histidine (His), and the agonist of the H(3) receptor (R)-alpha-methylhistamine (RAMH), on acquisition and retention of spatial reference memory in rats. Treatment with RAMH (10 mg/kg i.p.) facilitates recovery of spatial memory. In contrast, administration of His (500 mg/kg i.p.) does not affect the performance of this task. Moreover, pharmacological modulation of the cerebral histaminergic system does not impair the animals behavioral flexibility, i.e. their ability to adapt to a new learning task in the same stimular context. Improved retention of spatial memory after a reduction in cerebral histamine confirms the modulating role of this neurotransmitter in memory processes.

UNBIASED ESTIMATION OF THE TOTAL NUMBER OF NERVOUS CELLS AND VOLUME OF MEDIAL MAMMILLARY NUCLEUS IN HUMANS

In this study, we demonstrate that aging does not provoke any changes in neuronal number or in the glial cells of the medial mammillary nucleus (MMN) in humans. Three age groups were used: young (age 17-35), adult (age 50-57), and aged (age 70-88). Furthermore, no age-dependent volumetric changes were observed in the MMN. All the estimations were performed with stereological methods: an optical fractionator and Cavaliers principle. The total number of neurons cells was estimated using an optical fractionator and amounted to 32x10(3) in the young group, 24x103 in the adult group, and 29x103 in the aged group. The number of glial cells was 164x10(3), 187x103, 185x103, respectively. Thus, all three age groups had a neuron/glial ratio of about 1:5, 1:8, and 1:6, respectively. The MMN volume was estimated using the Cavaliers principle. The total volume was 6.98 mm3 in the young group, 6.66 mm3 in the adult group, and 6.80 mm3 in the aged group. We have demonstrated that neither the total number of neurons and glial cells nor the volume of MMN are affected by age.

Effects of histamine precursor and (R)-α-methylhistamine on the avoidance response in rats

The aim of this work is to clarify the role of histamine in learning and memory processes. In order to do this, the effect of administration of the histamine precursor, l-histidine (HIS) and of the agonist of the H3 receptor, (R)-α-methylhistamine (RAMH), on active avoidance response in rats is studied. Treatment with RAMH (10 mg/kg i.p.) increased the number of avoidance responses produced during acquisition and retention of the learning. In contrast, administration of l-his (500 mg/kg i.p.) impairs performance in the shuttle-box. These results are consistent with a role for histamine in cognitive processes and suggest that a increase in cerebral histamine levels impair the acquisition of avoidance response, whereas reduced levels facilitate this acquisition.

Age-related changes of the nucleolar organizer regions without neuron loss in medial mamillary bodies (hypothalamus) in old rats

Age-related morphological and functional changes were studied in the medial mamillary nuclei of the hypothalamus (MMN). The number of nerve cells and the volume of MMN were estimated in both groups of Wistar rats, adult and old (3 and 22 months, respectively) using stereologic methods such as the optical fractionator and Cavalieris method respectively. The number of neurons and glial cells remain inalterable with ageing but there was an age-dependent reduction in MMN volume. In the second experiment, functional changes in the MMN neurons were observed although there was no loss in neuron number. Several functional parameters of the Ag-NORs were quantified by a computer analysis system: area and number of Ag-NORs per neuron; number of neurons with one or several Ag-NORs and also surface of neuronal nucleus. The present study shows how ageing causes volumetric and functional changes in the MMN whereas the number of neurons and glial cells remain unchanged in the mamillary region. All these results confirm the effects of age on proteic synthesis activity in neurons of the MMN, showing a decreased neuronal activity in this region.

Non-effects of mammillary body lesions on spontaneous alternation: pre and postoperative study.

This study was designed to investigate the potential effects of medial mammillary nucleus (MMn) lesions on spontaneous alternation behavior in rats. Behavioral measurements were made in a water T maze in which the side arms were not differentially reinforced. Spontaneous alternation was tested before and after surgery alone. In both experiments, volumetric estimates of the MMn lesion were made by stereologic calculations. The results obtained do not support the direct participation of the MMn in retrograde or anterograde memory processes related to spontaneous spatial alternation.

043.20 HISTAMINE and SPATIAL MEMORY

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Active avoidance conditioning in rats: absence of sex difference and estrous effect

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