Dorsal hippocampal lesions boost performance in the rat sequential reaction time task.

It is commonly accepted that the hippocampus plays a major role in declarative memory across species and that it is of particular relevance for spatial memory in rodents. However, the interplay between hippocampal function and nondeclarative memory systems, such as procedural stimulus-response (S-R) or sequential learning, is less clear: depending on task requirements, an interaction, dissociation or interference between hippocampal function and other memory systems may occur. This study was conducted to investigate the influence of dorsal ibotenic hippocampal lesions on learning and performance of sequential behavior in a rat version of the serial reaction time task (SRTT). Magnetic resonance imaging (MRI) analyses of the lesions revealed a bilateral volume reduction of ≈ 46% (histological analyses: ≈ 59%) of the total hippocampus. They were largely confined to its dorsal part and led to an expected spatial memory deficits in an object place recognition test as compared to healthy controls, even though sham lesions had the same effect. Our earlier studies on sequential learning had revealed substantial impairments in case of dorsal striatal dopaminergic lesions. In the present study, however, hippocampal lesioned animals unexpectedly showed superior performance throughout SRTT testing and training as compared to controls, which resulted in a higher degree of subsequent automated sequential behavior. Thus, our data reveal the infrequent case where hippocampal lesions lead to long-term improvements in test performance of a type of rather complex procedural behavior. One possible explanation for this effect is that hippocampal activity in rodents can interfere with other memory systems during the acquisition of procedural tasks with very low spatial requirements, as used here. Alternative explanations for the observed superior SRTT performance in lesioned animals, such as hyperactivity or increased exploratory drive are also topic of the discussion.

Acquisition and performance in a rat sequential reaction time task is not affected by subtotal ventral striatal 6-OHDA lesions.

Based on findings of experiments with humans, non-human primates and rodents, it is commonly accepted that dopaminergic basal ganglia processes play a crucial role in procedural and sequential learning. Primal evidence for this hypothesis came from serial reaction time tasks (SRTT) studies, demonstrating that healthy controls show increased reaction times when visual stimulus presentation switches from a previously learned sequence to random stimulus presentation. This so-called interference effect was reduced in patients with Parkinson's disease. Since ethical and methodical aspects limit neurobiological research in human subjects, we developed a rat version of the human SRTT, which can be used to study experimentally induced brain damage. In the present experiment we investigated the effects of bilateral 6-OHDA lesions of the ventral striatum on sequential learning. The lesions led to subtotal dopaminergic depletions in the ventral striatum (58-60%) and also minor depletions in the medial neostriatum (32-46%). These lesions impaired task acquisition only moderately and did not worsen sequential performance since lesion and control animals showed a comparable interference effect when the trained sequence was tested against random stimulus presentation or violated sequences. In contrast, in an earlier SRTT experiment with medial neostriatal dopaminergic lesions (58-66%), the lesion animals were clearly impaired in their sequential learning as compared to controls. Therefore, we assume that subtotal dopamine loss in the medial neostriatum, rather than the ventral striatum, has a substantial effect on sequential learning.