Functional convergence of dopaminergic and cholinergic input is critical for hippocampus-dependent working memory.
Författare
Summary, in English
Although Parkinson's disease is a movement disorder, in many patients cognitive dysfunction is an important clinical sign. It is not yet clear whether this is attributable solely to a decrease in dopamine levels, or whether other neurotransmitter systems might be involved as well. In the present study, the importance of the mesocorticolimbic dopamine pathway and a possible convergence with forebrain cholinergic projections to neocortex and hippocampus in the regulation of learning and memory abilities were investigated by using specific lesion paradigms in one or both systems. Lesioning of dopaminergic neurons in the ventral tegmental area resulted in an impaired performance in the reference memory task, whereas the execution of the working memory tasks appeared to be unaffected in the Morris water maze. Analysis of the swim paths revealed that the dopamine-depleted animals were capable of adapting a search strategy on a given testing day but failed to transfer this information to the next day, suggesting a deficit in information storage and/or recall. In contrast, cholinergic lesions alone were without effect in all test paradigms. However, when both dopamine and acetylcholine were depleted, animals were also impaired in the working memory task, indicating that a functional convergence of the inputs from these systems was critical for acquisition of spatial memory. Interestingly, such an additional acquisition deficit appeared only after hippocampal cholinergic depletion regardless of a concurrent disruption of basalo cortical cholinergic afferents. Thus, further analyses of cholinergic alterations may prove useful in better understanding the cognitive symptoms in Parkinson's disease.
Publiceringsår
2008
Språk
Engelska
Sidor
7797-7807
Publikation/Tidskrift/Serie
The Journal of neuroscience : the official journal of the Society for Neuroscience
Volym
28
Issue
31
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Society for Neuroscience
Ämne
- Neurosciences
Nyckelord
- Nerve Degeneration: physiopathology
- Memory: physiology
- Maze Learning: physiology
- Hippocampus: physiology
- Cholinergic Fibers: physiology
- Dopamine: physiology
- Neural Pathways: physiology
Status
Published
Forskningsgrupp
- Brain Repair and Imaging in Neural Systems (BRAINS)
ISBN/ISSN/Övrigt
- ISSN: 1529-2401