Sandro Fagioli

Spatial learning in two inbred strains of mice : genotype-dependent effect of amygdaloid and hippocampal lesions

Spatial learning performance and maze-running strategies were estimated in two inbred strains of mice, C57BL/6 and DBA/2, submitted to an 8-arm radial maze task. Subsequently the genotype-dependent effect of hippocampus and amygdala on the mastering of this task was examined as a function of the different acquisition model provided by each strain. The results firstly show that unoperated C57BL/6 mice reach a higher level of performance and develop a stronger preference for adjacent arms - 45 degrees angle - turns than unoperated DBA/2 mice. In the high learner C57BL/6 strain, both hippocampal and amygdaloid lesions impair performance and modify maze-running strategies. With practice, however, the difference between amygdala-lesioned mice and controls disappears while that between hippocampus-lesioned mice and controls persists. Conversely, in the low learner DBA/2 strain, hippocampal lesions have a negative effect on a single parameter of performance, while amygdaloid lesions only affect maze-running strategies. Taken together, these results confirm the specific control exerted by the hippocampus on spatial learning. Moreover, they suggest that the amygdala can parallel the role of the hippocampus as far as the baseline level of performance of the strain considered is high.

Radial maze performance and open-field behaviours in aged C57BL/6 mice: Further evidence for preserved cognitive abilities during senescence

C57BL/6 mice, aged 2 or 24 months, were tested in a radial maze and observed for an 8-min period, repeated on 3 consecutive days, in an open-field situation with a novel object. In the eight-arm maze, the number of unrepeated path choices made by old mice does not significantly increase with training, whereas it does in young mice. Older animals also take significantly longer to solve the task but the two age groups do not differ with respect to how many paths they run before making the first error or in the strategies used to solve the task. In the open-field situation, the two age groups differ with regard to grooming and rearing behaviour, while in the novelty situation, older animal show a higher level of locomotor activity, perform less freezing, and interact more with the novel object. Habituation curves for all parameters, except grooming in the open field, do not differ between the two groups, thus indicating that this form of nonassociative learning does not vary substantially with increasing age. Results are discussed in terms of preserved cognitive abilities during senescence in that strain.

Effects of oxotremorine on inhibitory avoidance behaviour in two inbred strains of mice: interaction with 5-methoxy-NN-dimethyltriptamine

The effects of the cholinergic muscarinic agonist, oxotremorine (0.005, 0.01, 0.02 and 0.04 mg/kg), the serotonergic agonist, 5-methoxy-NN-dimethyltriptamine (5-MeODMT) (0.5, 1 and 2 mg/kg), and their combination, were investigated in C57BL/6 and DBA/2 mice using a one-trial inhibitory avoidance task, drug treatment being given immediately after the acquisition trial. Post-trial administration of oxotremorine facilitated, while post-trial administration of 5-MeODMT inhibited memory retention of both strains in a dose-dependent fashion. The DBA/2 strain was more affected by oxotremorine than the C57BL/6 mice; no strain-dependent sensitivity to serotonergic agonist administration was observed. In both strains, the combination of oxotremorine plus 5-MeODMT inhibited the performance improvement shown by the administration of the cholinergic agonist alone. The facilitatory role of cholinergic stimulation on retention performance was confirmed and an inhibitory action of the serotonergic system on memory processes was suggested. Moreover, the present results support a functional interaction between cholinergic and serotonergic systems on memory consolidation.

Genotype-dependent involvement of limbic areas in spatial learning and postlesion recovery

Male C57BL/6 (C57) and DBA/2 (DBA) mice with hippocampal, amygdaloid, or sham lesions were tested in a radial eight-arm maze 1 or 4 weeks after surgery. The results show that the effect of the lesions varied according to the performance level of the strain considered. In the high-learner C57 strain, the two lesions impaired acquisition at both postlesion intervals. Conversely, in the low-learner DBA strain, only hippocampal lesions impaired acquisition 1 week but not 4 weeks after lesioning. It is hypothesized that if more limbic areas are involved in controlling spatial learning in C57 mice, these structures could be processing distinct but complementary memory attributes, thus contributing to a high baseline performance. This, however, also entails an increased sensitivity of C57 performance to brain damage with reduced possibilities of long-term recovery.

Developmental differences of antinociceptive effects of oxotremorine in two inbred strains of mice

During development the C57BL/6 and DBA/2 mouse strains present morphological variations in cholinergic forebrain structures correlated with different behavioral reactivities to cholinergic agents. The present research assessed that these strain-dependent differences are also present in cholinergic-mediated analgesia. The administration of oxotremorine (0.0025, 0.005 and 0.01 mg/kg) to 30- and 60-day-old C57 and DBA mice resulted in dose- age- and strain-dependent analgesia. In particular oxotremorine is more effective in DBA/2 than in C57BL/6 mice and the latter strain showed a significant decrease of analgesic response in adulthood.

Open field behaviours and spatial learning performance in C57BL/6 mice: early stage effects of chronic GM1 ganglioside administration

One month intact C57BL/6 mice were treated with GM1 ganglioside for 3 consecutive weeks. At 2 months of age, treated and control mice were observed in the open-field situation and tested for spatial learning in a radial eight-arm maze. The results showed that, in the open-field, treated mice displayed less freezing but more rearing behavior than control animals. In the radial maze, GM1-treated mice made more correct path choices before the first error within each trial than control mice. However, this improvement was limited to the first stage of training. These results suggest an early stimulating effect of the GM1 ganglioside treatment which could facilitate adaptive reactions to new situations.

Effect of chronic GM1 ganglioside administration on passive avoidance retention in mice

Chronic administration of GM1 ganglioside to C57BL/6 mice during development improved passive avoidance retention. A significant weight increase was also evident in the treated animals in comparison with the control group. The results are discussed in terms of the possible effects exerted by GM1 upon the cholinergic mechanisms of this inbred strain.

Chronic administration of phosphatidylserine during ontogeny enhances subject-environment interactions and radial maze performance in C57BL/6 mice

A longitudinal behavioral study was performed in mice exposed to the bovine brain phospholipid phosphatidylserine (BC-PS) from birth until sixty days. Examination of treated and control pups revealed no effect of the treatment on body weight nor on sensorimotor reflexes. At one and two months of age, when placed in an open field and, particularly, in the presence of a novel object, treated mice were found more interactive with their environment than control mice. Finally, when submitted to a radial eight-arm maze problem, choice accuracy was higher and maze-running strategies more adaptive in treated than in control adult mice. These results suggest a stimulating effect of the treatment on subject-environment interactions during ontogeny underlying improved cognitive abilities in adulthood.

Phosphatidylserine administration during postnatal development improves memory in adult mice

Postnatal administration of an aqueous suspension of phosphatidylserine (BC-PS) to C57BL/6 mice resulted in improvement of memory processes in adulthood, as assessed in a passive avoidance task. These findings are discussed in terms of the effects of BC-PS on cholinergic mechanisms and of cholinergic patterns of this inbred strain.

Dose-dependent effect of GM1 ganglioside during development on inhibitory avoidance behaviour in mice : influence of the period of administration

Groups of C57BL/6 mice were injected intraperitoneally with GM1 monosialoganglioside at different ages during development and subsequently tested for the retention of an inhibitory avoidance task 24 h after training. Results show improvements in inhibitory avoidance retention according to the age of the animals, the doses of GM1 used and the length of treatment. The effective doses ranged from 20 mg/kg for all age groups after 7 days treatment to 280 mg/kg for 6- and 7-week old animals after pre-trial treatment. Six- and 7-week-old mice are more sensitive to GM1 treatment than 5-week-old animals and, with decreasing lengths of treatment, increasing doses of GM1 are needed to improve the performance of the animals. These findings show that short treatment durations can be effective in improving inhibitory avoidance retention as long as the doses of GM1 administered are increased and that animals are more sensitive to the treatment when they are 6 or 7 weeks of age than when they are 5 weeks old.