ABSTRACT
The substantia nigra pars compacta (SNc) and the dorsal striatum are often considered to be necessary for stimulus-response (S-R) habit learning, whereas the dorsal hippocampus is considered to be necessary for relational (declarative) memory. Spatial learning is a kind of relational learning that occurs when a rat is released from different locations (variable start) in a water maze to find a submerged platform that is kept in a constant location. However, when the rat is always released from the same starting position (constant start), it can learn to find the platform oriented by a fixed configuration of cues, that is, by S-R learning. To test the critical role of the SNc in S-R and relational learning, the authors tested adult male Wistar rats, sham-operated or with a lesion in the SNc, in these 2 versions of the water maze task. The SNc lesion was induced by bilateral intranigral infusion of 0.5 micromol 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine. Although the SNc-lesioned rats learned the variable-start version as effectively as sham rats did, they were significantly impaired in learning the constant-start version of the task.
Subject(s)
Maze Learning/physiology , Spatial Behavior/physiology , Substantia Nigra/physiopathology , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology , Analysis of Variance , Animals , Behavior, Animal , Biogenic Monoamines/metabolism , Immunohistochemistry/methods , Male , Maze Learning/drug effects , Neurotoxins/pharmacology , Rats , Rats, Wistar , Reaction Time/drug effects , Spatial Behavior/drug effects , Substantia Nigra/injuries , Swimming , Time FactorsABSTRACT
Adult male Wistar rats with a substantia nigra pars compacta (SNc) lesion induced by intranigral administration of 1 micromol 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were used as a model of early phase Parkinson's disease (PD). This lesion caused a partial depletion of striatal dopamine (DA). The animals were submitted to a spatial working memory version of the water maze task in which they had to find a hidden (submersed) platform using online-maintained information that the platform remains in the same place during four consecutive trials, but that it is moved to another place every training day. Left, but not right SNc-lesioned rats were impaired in finding the platform in the second trial. This result suggests that the left SNc plays a key role in spatial working memory. Control experiments ruled out the possibility that motor impairment, sensory neglect, and/or impairment in the mental representation of the contralateral spatial environment had affected performance of the SNc-lesioned rats.
