José Manuel Cimadevilla

Inactivating one hippocampus impairs avoidance of a stable room-defined place during dissociation of arena cues from room cues by rotation of the arena

Unilateral intrahippocampal injections of tetrodotoxin were used to temporarily inactivate one hippocampus during specific phases of training in an active allothetic place avoidance task. The rat was required to use landmarks in the room to avoid a room-defined sector of a slowly rotating circular arena. The continuous rotation dissociated room cues from arena cues and moved the arena surface through a part of the room in which foot-shock was delivered. The rat had to move away from the shock zone to prevent being transported there by the rotation. Unilateral hippocampal inactivations profoundly impaired acquisition and retrieval of the allothetic place avoidance. Posttraining unilateral hippocampal inactivation also impaired performance in subsequent sessions. This allothetic place avoidance task seems more sensitive to hippocampal disruption than the standard water maze task because the same unilateral hippocampal inactivation does not impair performance of the variable-start, fixed hidden goal task after procedural training. The results suggest that the hippocampus not only encodes allothetic relationships amongst landmarks, it also organizes perceived allothetic stimuli into systems of mutually stable coordinates. The latter function apparently requires greater hippocampal integrity.

Spatial memory alterations in three models of hepatic encephalopathy.

A behavioural evaluation was carried out on three chronic models of hepatic encephalopathy: two models of type B HE, portacaval shunt (PCS) and portal hypertension (PH) and one of type C HE with cirrhosis and portal hypertension from thioacetamide intoxication (TAA). The tasks selected cover a wide range of behaviours related to: locomotion (rotarod-accelerod test), anxiety (open field and elevated plus maze) and memory (Morris water maze). The results indicate that neither locomotor activity nor anxiety was affected in our models, in comparison with their respective controls. However, this is not the case for the mnesic tasks. Hence, the PCS and TAA groups displayed a severe alteration in spatial reference memory and cannot correctly perform the Morris maze task, while this alteration is less severe in the PH group. On the contrary, the PH group revealed a deficit in spatial working memory, like the TAA group, but this does not occur in subjects with PCS. These results reveal a double dissociation in spatial reference memory and spatial working memory between the PCS and PH groups, which would be of great interest to study about cerebral causes and substrates of the alterations accompanying HE.

A new virtual task to evaluate human place learning

This study assesses the effectiveness of a new virtual task to evaluate human place learning. This test was based on the hole-board maze, developed for rodent research. Its design provides an easy set of levels of difficulty. Sixty-three undergraduate students (30 men and 33 women) were randomly distributed into three testing conditions; they had to find 3, 5 and 7 rewards, respectively, in a virtual room with 16 possible rewarded positions. Subjects were asked to use the minimum amount of attempts to discover all the rewards in 10 trials. In the initial trial subjects needed to visit almost all the positions to discover the rewards. However, in the last trial an important percentage of subjects did not err. Results showed that all subjects acquired the task but with different amounts of mistakes directly related to the level of difficulty of the condition. In addition, women were slower and less accurate than men. These results agree with previous results in other virtual tasks, and support the spatial component of this test.

Influence of gonadal steroids on the glial fibrillary acidic protein‐immunoreactive astrocyte population in young rat hippocampus

It is known that expression of glial fibrillary acidic protein (GFAP) as an astrocyte‐specific marker can be regulated by levels of circulating gonadal steroids during postnatal development. In addition, astrocytes play an important role in the physiology of the hippocampus, a brain region considered sexually dimorphic at the neuronal level in rodents. To evaluate the contribution of glial cells to gender‐related differences in the hippocampus, we estimated the number of GFAP‐immunoreactive (GFAP‐IR) astrocytes in the hippocampus (CA1 and CA3 areas, dorsal and ventral regions) of male and female rats aged 30 days. Groups of 30‐day‐old masculinized females (TP‐females; injected with testosterone propionate at birth) and feminized males (FLU‐males, castrated and treated with flutamide, an androgen receptor antagonist) were included to assess the effects of gonadal hormones on these hippocampal astrocytes. Using the optical fractionator method, the total number of GFAP‐IR cells found in CA1 and CA3 areas was significantly higher in males compared to that in age‐matched females. This numerical pattern was reversed in TP‐females and FLU‐males in both hippocampal areas. In addition, more GFAP‐IR cells were found in dorsal hippocampus than in the ventral region in the CA1 area from all experimental groups, whereas this result was found in the CA3 area from males and TP‐females. Our results suggest an essential contribution of gonadal hormones to gender differences found in the astrocyte population of the rat hippocampus during development.

Developmental gender differences in children in a virtual spatial memory task.

OBJECTIVE Behavioral achievements are the product of brain maturation. During postnatal development, the medial temporal lobe completes its maturation, and children acquire new memory abilities. In recent years, virtual reality-based tasks have been introduced in the neuropsychology field to assess different cognitive functions. In this work, desktop virtual reality tasks are combined with classic psychometric tests to assess spatial abilities in 4- to 10-year-old children. METHOD Fifty boys and 50 girls 4-10-years of age participated in this study. Spatial reference memory and spatial working memory were assessed using a desktop virtual reality-based task. Other classic psychometric tests were also included in this work (e.g., the Corsi Block Tapping Test, digit tests, 10/36 Spatial Recall Test). RESULTS In general terms, 4- and 5-year-old groups showed poorer performance than the older groups. However, 5-year-old children showed basic spatial navigation abilities with little difficulty. In addition, boys outperformed girls from the 6-8-year-old groups. Gender differences only emerged in the reference-memory version of the spatial task, whereas both sexes displayed similar performances in the working-memory version. CONCLUSION There was general improvement in the performance of different tasks in children older than 5 years. However, results also suggest that brain regions involved in allocentric memory are functional even at the age of 5. In addition, the brain structures underlying reference memory mature later in girls than those required for the working memory.

Virtual reality tasks disclose spatial memory alterations in fibromyalgia

OBJECTIVE The objective is to assess performance on virtual reality spatial memory tasks as well as classical neuropsychological tests in patients with fibromyalgia (FM). METHODS Fifteen FM patients and fifteen healthy age- and education-matched controls performed the virtual versions of the Morris water maze and the hole board (a virtual version called Boxes room). All participants also completed a comprehensive neuropsychological evaluation that included measures of general intelligence, attention/working memory and visuospatial memory. RESULTS Both virtual reality tasks were demonstrated to be sensitive to spatial memory alterations. FM patients performed significantly worse than controls in the spatial navigation tasks, showing significantly more errors than their matched controls, while no significant differences were found between patients and controls regarding standard neuropsychological testing. In addition, those FM patients with longer chronicity had lower auditory memory span, visuospatial memory and general intelligence within their group. CONCLUSION These results are the first to demonstrate that there is a spatial learning deficit in people with FM, which suggest that the hippocampal system can be disturbed in this syndrome.

NOR activity in hippocampal areas during the postnatal development and ageing

The silver staining of the nucleolar organizer regions (Ag-NORs) was used in order to estimate the biosynthetic activity of three hippocampal areas (dentate gyrus, CA1 and CA3) during postnatal development and ageing. 32 Wistar rats were used and 4 groups were formed according to the age of the animals (14, 21, 90 days and 23 months). Several Ag-NOR parameters such as mean Ag-NOR area and the ratio between Ag-NOR and nuclear areas per neuronal cell were quantified using an image analysis system. High values of these parameters are associated with a high rate of rRNA transcription. In this way, the neural biosynthetic activity in all regions studied decreased as the older ages are reached. Differences between areas are shown with the dentate gyrus and CA1 areas decreasing faster. The different activity among these areas is discussed, taking into account the particular affect on these areas of some injuries and the ageing process. Our results support the hypothesis of NOR loss as a main cause of ageing as reported by other authors.

Unilateral hippocampal blockade reveals that one hippocampus is sufficient for learning a passive avoidance task

Understanding hippocampal participation in memory processes is one of the goals in neuroscience research. By blocking the hippocampus unilaterally in Wistar rats, we assessed the contribution of this brain structure to memory in a passive avoidance task. Subjects were distributed into four groups. Group 1 received tetrodotoxin (TTX) in the right hippocampus during acquisition and retrieval phases. Group 2 had the same procedure as group 1, except that the contralateral hippocampus was blocked during retrieval. Subjects from group 3 acquired the task with saline (both hippocampi intact) and retrieved with the right hippocampus inactivated. Finally, group 4 received TTX unilaterally 2 min after acquisition to determine the hippocampal role in consolidation. Results showed that group 2 was impaired, compared with the other groups, during retrieval. These findings reveal that the hippocampal contribution to this task differs from that in other tasks considered to be hippocampus dependent.

Age and gender-related differences in a spatial memory task in humans

Cognitive skills decline with age. Our ability to keep oriented in our surrounding environment was demonstrated to be influenced by factors like age and gender. Introduction of virtual reality based tasks improved assessment of spatial memory in humans. In this study, spatial orientation was assessed in a virtual memory task in order to determine the effect of aging and gender on navigational skills. Subjects from 45 to 74 years of age were organized in three groups (45-54, 55-64, 65-74 years old). Two levels of difficulty were considered. Results showed that males outperformed females in 65-74 years-old group. In addition to this, females showed a more noticeable poor performance in spatial memory than males, since memory differences appeared between all age groups. On the other hand, 65-74 year-old males showed an impaired performance in comparison with 45-54 year-old group. These results support that spatial memory becomes less accurate as we age and gender is an important factor influencing spatial orientation skills.

Hippocampal heterogeneity in spatial memory revealed by cytochrome oxidase

The oxidative metabolism was assessed in the septal, intermediate and temporal hippocampus in Wistar rats that were trained following a working memory schedule in the Morris water maze. The cytochrome oxidase histochemistry was measured at 90 min, 6, 24 and 48 h post-training. We found an increase in the septal dentate gyrus at 90 min, at 6h the increase was also found in CA3 and CA1 regions and returned to basal levels at 24h. In contrast, the intermediate region showed lower increase, limited to the dentate gyrus and CA3 at 24h post-training. No changes were found in the temporal hippocampus. These findings suggest that septal and intermediate hippocampal zones participate in this spatial learning and contribute at different moments to process this information.