Rubén Miranda

c-Fos expression in supramammillary and medial mammillary nuclei following spatial reference and working memory tasks.

To investigate brain substrates of spatial memory, neuronal expression of c-Fos protein was studied. Two groups of rats were trained in two spatial memory tasks in the Morris water maze, where the rats have to apply a reference memory rule or a working memory rule. In addition to the experimental groups, two control groups were used to study c-fos activation not specific to the memory processes studied. After immunohistochemical procedures, the number of c-Fos positive neuronal nuclei was quantified in the mammillary body (MB) region (medial mammillary nucleus [MMn] and supramammillary nucleus [SuM]). The results have shown that some MMn neurons expressed c-Fos nuclear immunoreactivity related to spatial working memory but not to spatial reference memory. The increased number of c-Fos immunoreactive neuronal nuclei in the SuM was related to spatial training but not to either working or reference memory demands of the tasks.

Effects of medial prefrontal cortex lesions on anxiety-like behaviour in restrained and non-restrained rats.

The medial prefrontal cortex has been associated with fear, anxiety and stress regulation, and has recently been suggested to play a crucial role in the development of behavioural changes in response to stress. In this study, we evaluated medial prefrontal cortex (mPFC) involvement in both anxiety-like behaviour and increased anxiety-like responses induced by uncontrollable restraint. Rats with mPFC electrolytic lesions (n=7) and sham-lesioned (n=8) were tested in the elevated T-maze (ETM). Restrained rats with mPFC lesions (n=8) and sham-lesioned rats (n=6) were tested in the elevated T-maze 24h after restraint. Both two-trial passive avoidance and one-trial escape behaviours were assessed. The results revealed that mPFC lesions impair passive avoidance, but not escape behaviour. In addition, decreased anxiety-like behaviour in both passive avoidance and escape behaviours were observed in restrained rats with mPFC lesions. Our results suggest that mPFC is important in mediating both anxiety-like behaviour expression and long-term anxiogenic-like effects induced by acute restraint.

Hippocampal and caudate metabolic activity associated with different navigational strategies.

Hippocampal and striatal systems are widely related to spatial tasks. Depending on the strategies used, different memory systems can be activated. In this study, the authors used the cytochrome c-oxidase technique as a functional marker of the hippocampal and dorsal striatum activity related to training in several water maze tasks. Current results show a differential participation of the hippocampal and striatal systems in navigation. When spatial information is relevant, participation of the hippocampal system is more important, and when the task is similar to a response learning one, the striatal system is more active. According to computational models, CA3 seems to be more active when the associative demand is higher, whereas CA1 and dentate gyrus activity are higher when spatial information processing is required.

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.

Bilateral and Unilateral Hippocampal Inactivation Did not Differ in their Effect on Consolidation Processes in the Morris Water Maze

Consolidation processes were studied in the rat by using functional inactivation techniques. Previous results showed that unilateral hippocampal inactivation alters consolidation. It is not clear if bilateral treatments increase the impairment. Wistar rats were trained in the Morris water maze during 4 consecutive days. Subjects received saline or tetrodotoxin in the dorsal hippocampus 1 min after training. Results showed that bilateral as well as unilateral treatments impair consolidation to the same degree, as shown by the mean latency to reach the platform. In both cases, the impairment is only visible in the first trial of the session following the blockade.

Functional sex differences in the accessory olfactory bulb of the rat.

The aim of this study is to determine whether sex-related differences exist in the biosynthetic activity of the mitral cells within the mitral layer of the AOB. Possible functional changes over the estrus cycle and the potential effects of castration and androgenization are assessed. Biosynthetic activity was measured using silver staining of the argyrophilic proteins associated with the nucleolar organizer regions (Ag-NOR). Assisted by stereological methods, the following parameters were studied: mean number, percentage and mean area of Ag-NOR in estrus and diestrus females, intact males, castrated and androgenizated rats. We detected sex differences in a histochemical marker related to synthetic activity, an estrus cycle effect and changes resulting from the perinatal treatments. We conclude that this structurally dimorphic region is also functionally dimorphic.

Astroglial distribution and sexual differences in neural metabolism in mammillary bodies.

The sexual differences in cerebral nuclei are produced by the organizational and the activational function of gonadal hormones. The different performances by male and female rats in memory tasks requiring use of the mammillary bodies (MBs), could be due to structural and functional sexual dimorphic differences. Our work quantifies the number of glial fibrillary acidic protein immunoreactive (GFAP-IR) astrocytes, and neuronal metabolic activity measured by the cytochrome oxidase (CO) histochemistry in the MBs in rats of both sexes. We find that there is no difference in astroglial number in the medial mammillary nucleus (MMN) and in the lateral mammillary nucleus (LMN) of males, females in estrus and diestrus adult rats. However, we do find statistically significant differences between the sexes in the neuronal oxidative metabolism influenced by the estrous cycle. We, therefore, conclude that there are functional and not structural sex differences in the MBs.

Prehepatic Portal Hypertension Induces Alterations in Cytochrome Oxidase Activity in the Rat Adrenal Gland

One approach to assess neuroendocrine response to portal hypertension in short-term portal vein-stenosed rats consists in studying metabolic and functional activity patterns in adrenal glands using mitochondrial enzyme cytochrome c oxidase (COX) as a histochemical marker. Male Wistar rats were divided into two groups: a control group (Group I; n = 8), in which the animals did not undergo any operative intervention, and a triple calibrated portal vein stenosis group (TPVS) (Group II; n = 7). The sections of suprarenal glands were histochemically stained for COX and the optical densitometry was measured by a computer image analyzer attached to a microscope. In TPVS rats, COX activity in the adrenal gland cortex is lower than in control rats and affects the fascicular (52.30, 47.16–60.98, vs. 67.12, 60.31–73.89, p =. 002), glomerular (49.68, 46.19–53.56 vs. 70.47, 64.64–73.51, p <. 001), and reticular (47.35, 35.63–54.39, vs. 55.37, 49.76–58.97; p <. 05) layers. In contrast, COX activity in the adrenal gland medulla is similar in TPVS rats and in control rats (29.91, 29.54–31.18, vs. 29.67, 28.95–30.23). The changes in adrenocortical COX activity in short-term-TPVS rats could constitute a pathogenic factor for both splanchnic and systemic hyperdynamic circulations, described in this experimental model of prehepatic portal hypertension.