Time course of the elevation of nerve growth factor (NGF) content in the hippocampus and septum following lesions of the septohippocampal pathway in rats

Axotomy of cholinergic neurons in the medial septum-diagonal band and degeneration of their terminals in the hippocampus resulting from fornix-fimbria lesions induce elevation of NGF content in these two brain regions. Postlesion levels of cholinergic neuron-specific ChAT activity in the septum suggest that endogenously produced NGF may, at least partly, promote survival of axotomized cholinergic neurons or induce ChAT activity in undamaged cells or both. These findings thus support the proposed trophic role for NGF in central cholinergic neurons.     

Hippocampal serotonin re-uptake and nocturnal locomotor activity after microinjections of 5,7-DHT in the fornix-fimbria

The role of the hippocampal 5-hydroxytryptamine (5-HT) terminals in the control of locomotor activity was investigated by lesioning 5-HT axons in the fimbria with 5,7-dihydroxytryptamine (5,7-DHT). Rats pretreated with desimipramine (10 mg/kg, i.p.) received microinjections of 5,7-DHT (0, 1, 3, 5 or 10 μg in 0.4 μl ascorbic Ringer's solution) into the fornix-fimbria. On the fourteenth to twenty-first nights after operation, nocturnal locomotor activity was measured in photocell cages. Twenty-eight to thirty days after operation degeneration of 5-HT terminals was assessed by measuring in vitro [³H]5-HT re-uptake in slices of dorsal hippocampus, ventral hippocampus and the septum.Groups injected with 5,7-DHT showed hyperactivity in the night period and increased decrements of activity between tests, both of which were related to the dose of neurotoxin. A reduction of [³H]5-HT re-uptake was found in dorsal hippocampus which was related to the dose of 5,7-DHT, but ventral hippocampal and septal [³H]5-HT re-uptake were not systematically reduced. For each rat, levels of dorsal and ventral hippocampal [³H]5-HT re-uptake were negatively correlated with the mean nocturnal activity from the 7 nights of testing. Levels of dorsal, but not ventral hippocampal [³H]5-HT re-uptake were negatively correlated with the mean nightly decrement of activity. No correlations were found between septal [³H]5-HT and these activity measures. These results, indicate that the increase in nocturnal locomotor activity caused by generalized depletion of 5-HT in the brain may be due to disruption of hippocampal 5-HT terminals supplied by the fornix-fimbria.     

Septal transplants restore maze learning in rats with fornix-fimbria lesions

In a study of the capacity of neural grafts to promote functional recovery in rats with fimbria-fornix lesions, 5 groups of rats were studied behaviourally and with acetylcholinesterase (AChE) histochemistry: (1) sham-operated controls; (2) bilateral fimbria-fornix lesions; (3) bilateral lesions plus bilateral solid embryonic septal grafts to the lesion cavity; (4) bilateral lesions plus bilateral embryonic septal suspension injections into the hippocampus; and (5) bilateral lesions plus bilateral solid embryonic locus coeruleus grafts to the lesion cavity. Seven months were allowed for growth of the grafts and reinnervation of the host hippocampus prior to behavioural testing.The control rats were able to rapidly learn a rewarded alternation task, while the performance of animals with bilateral fimbria-fornix lesions alone remained at a chance level. Both types of septal grafts (rich in cholinergic neurones) but not the locus coeruleus grafts (rich in noradrenergic neurones) reversed the impairment. Behavioural recovery correlated significantly with AChE-positive fibre ingrowth from the grafts into the denervated host hippocampus. However, the septal grafts did not ameliorate the lesion-induced disturbances in spontaneous activity or spontaneous alternation. Thus, the observed behavioural recovery appears specific to the conditioned alternation task and dependent upon cholinergic reinnervation of the hippocampus.     

Systematic comparison of the effects of hippocampal and fornix-fimbria lesions on acquisition of three configural discriminations

The effects of lesions to the hippocampal system on acquisition of three different configural tasks by rats were tested. Lesions of either the hippocampus (kainic acid/colchicine) or fornix-fimbria (radiofrequency current) were made before training. After recovery from surgery, rats were trained to discriminate between simple and compound-configural cues that signaled the availability or nonavailability of food when a bar was pressed. When positive cues were present, one food pellet could be earned by pressing a lever after a variable time had elapsed. The trial terminated on food delivery (variable interval 15 s). This procedure eliminates some possible alternative explanations of the results of previous experiments on configural learning. Hippocampal lesions increased rates of responding and retarded acquisition of a negative patterning task (A⁺, B⁺, AB⁻); using a ratio measure of discrimination performance these lesions had a milder retarding effect on a biconditional discrimination (AX⁺, AY⁻, BY⁺, BX⁻), and they had no effect on a conditional context discrimination (X: A⁺, B⁻; Y: A⁻, B⁺). Fornix-fimbria lesions did not affect acquisition of any of these tasks but increased rates of responding. The results suggest that several task parameters determine the involvement of the hippocampus in configural learning; however, all tasks tested can also be learned to some extent in the absence of an intact hippocampal system, presumably by other learning/memory systems that remain intact following surgery. The lack of effect of fornix-fimbria lesions on any of these tasks suggests that retrohippocampal connections with other brain areas may mediate hippocampal contributions to the learning of some configural tasks. An analysis of these results and of experiments on spatial learning situations suggests that involvement of the hippocampus is a function of the degree to which correct performance depends on a knowledge of relationships among cues in a situation. Hippocampus 7:371–388, 1997. © 1997 Wiley-Liss, Inc.