1,720,998 research outputs found

    The induction of cyclic nucleotide phosphodiesterase 4 gene (PDE4D) impairs memory in a water maze task

    No full text
    In this study, the effects on memory of intraperitoneal post-training administration of cyclic nucleotide phosphodiesterase (PDE) inhibitors, DC-TA 46 and rolipram, were tested using a visible/hidden-platform water maze task. The effects of these compounds on cyclic nucleotide levels in the hippocampal formation (HF) and striatum (CP) were also assessed, by enzymatic immunoassay (EIA). The results obtained from rats trained in the visible-platform task were not significantly different from controls. On the contrary, the animals trained in the hidden-platform water maze task showed a memory impairment, when injected with DC-TA 46 at maximal dose of 20 mg/kg and with rolipram at 3 and 30 mg/kg doses. The effects of these drugs on cyclic nucleotide levels in HF and CP were observed at 30 min and at 24 h after drug administration. Thirty minutes after drug injection, we observed an increase of cAMP level, both in HF and in CP. Twenty-four hours after the retention test, we observed that in CP the cAMP intracellular level remained high, while in the HF at effective doses both inhibitors induced cAMP PDE activity, determining a decrease of cyclic nucleotide. Semi-quantitative RT–PCR analysis, together with Western blot immunodetection, showed a mRNA and protein induction of PDE4D PDE isoforms, that may account for the increase of PDE activity observed. Our data suggest that, despite cyclic nucleotide increase at 30 min, the fundamental event causing memory impairment, came from the subsequent long time decrease of cAMP levels, due to the post-translational PDE4D induction

    Motor skills and learning in the rats: role of the ponto-cerebellar pathway

    No full text
    Many evidences support the role of the cerebellum (Cb) in motor learning and memory. Previous studies showed that olivary projections to the Cb are involved in motor learning. Since the pontine nuclei are the other main relay in the cerebro-cerebellar pathway, our purpose is to verify the involvement of the ponto-cerebellar projection in motor skills and spatial learning, by comparing sham-operated animals and rats with selective lesion of the inferior olivary complex (IOC) or middle cerebellar peduncle (mcp). Two groups of male Wistar rats were used: in order to destroy the IOC, the first group was treated with 3-acetylpiridine (3-AP) i. p. ; the second group received electrolytic lesions of the mcp, to interrupt the ponto-cerebellar pathway. Different groups of lesioned and sham-operated animals were then submitted to 3 tasks: unrotated-rod, rota rod at 20 r. p. m., and Morris water maze (MWM). When trained on the unrotated-rod, either 3-AP-treated or mcp lesioned rats showed at the beginning some static equilibrium deficiencies but, with training, they were able to reach the maximal scores attained by the controls. The rats submitted to the rota-rod at 20 r. p. m. obtained scores significantly lower than the controls. In fact, they were unable to improve their performance by training. Therefore, our results suggest that either the lesion of the IOC or the lesion of the mcp prevent learning of complex motor sequences. Finally, the animals were submitted to a MWM (spatial version) : the results indicate that both the lesion of the IOC and mcp alter learning of spatial tasks. These findings show that both the ponto- and the olivo-cerebellar pathways are involved in learning complex motor sequences and spatial tasks. Since both projections converge onto Purkinje cells, our data suggest that motor learning is supported in the cerebellum by anatomical re-arrangement of synaptic interactions of Purkinje cells with both climbing and parallel afferent fiber
    corecore