Septal grafts improve acquisition of an operant timing task after fimbria-fornix lesions in rats: Role of the interval between lesion and transplantation surgeries.

In a previous study we evaluated the conditions under which septal grafts could ameliorate performance of rats with fimbria-fornix lesions in an operant differential reinforcement of low rates of responding (DRL) task. Although the best recovery was demonstrated by the group in which the grafts were made 10 days following the lesion surgery, this factor (lesion-graft interval) was confounded with the developmental stage of the donor tissue, and it was suggested that the age of the embryonic donor was a more significant factor than the lesion graft interval in achieving good recovery. The present study provides a better control of embryonic age of the donor tissues, and we report that cholinergic rich septal grafts implanted into the host hippocampus either immediately or 11 days following fimbria-fornix lesion yielded better recovery than when the grafts were implanted after longer (8 weeks) lesion-graft intervals. In addition, grafts implanted into the intact hippocampus were without significant effect when the host rats were subjected to a delayed fimbria-fornix lesion made 10 weeks after graft implantation. These results corroborate the hypothesis of Nieto-Sampedro, Manthorpe and colleagues that 'wound-derived neurotrophic factors' can promote the functional viability of embryonic septal grafts in the hippocampus, even if such factors are not absolutely necessary for graft survival.

Unilateral dopamine lesions in neonatal, weanling and adult rats: comparison of rotation and reaching deficits.

The aim of this study was to compare the functional effects of neonatal, weanling and adult lesions of the dopaminergic (DA) mesencephalic neurones on paw-reaching behaviour. The mesotelencephalic DA pathway was destroyed unilaterally in neonatal (3 and 7 day), weanling (21 day) and adult (2 months) rats by local injection of 6-hydroxydopamine into the medial forebrain bundle at the level of the lateral hypothalamus, followed by behavioural studies conducted 2 months later. Amphetamine and apomorphine induced similar rates of rotation irrespective of the age of the lesion. By contrast skilled reaching with the contralateral paw was profoundly disrupted by lesions made in adult or weanling rats, but a much reduced deficit was observed in neonatally lesioned rats. Tyrosine hydroxylase immunohistochemistry indicated a similar degree of dopamine cell loss from the substantia nigra in all groups. These observations suggest that the host brain undergoes developmental changes 1-3 weeks postnatally that influence the long-term effects of lesions in the nigrostriatal dopamine system.

Cholinergic blockade in prefrontal cortex and hippocampus disrupts short-term memory in rats.

The muscarinic antagonist scopolamine was injected into the prefrontal cortex and hippocampus of rats that were well trained in an operant delayed non-matching to position task. Cholinergic antagonism in the hippocampus induced dose- and delay-dependent deficits, characteristic of impaired short-term retention. By contrast, cholinergic antagonism in the prefrontal cortex induced dose-dependent but delay-independent deficits, suggesting disturbance of some non-mnemonic regulatory process in the neocortex.