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Functional convergence of dopaminergic and cholinergic input is critical for hippocampus-dependent working memory.

Wisman, Liselijn LU ; Sahin, Gurdal LU ; Maingay, Matthew LU ; Leanza, Giampiero LU and Kirik, Deniz LU (2008) In The Journal of neuroscience : the official journal of the Society for Neuroscience 28(31). p.7797-7807
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Nerve Degeneration: physiopathology, Memory: physiology, Maze Learning: physiology, Hippocampus: physiology, Cholinergic Fibers: physiology, Dopamine: physiology, Neural Pathways: physiology
in
The Journal of neuroscience : the official journal of the Society for Neuroscience
volume
28
issue
31
pages
7797 - 7807
publisher
Society for Neuroscience
external identifiers
  • wos:000258061600009
  • pmid:18667612
  • scopus:50349102902
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.1885-08.2008
language
English
LU publication?
yes
id
81e64a98-bb71-41f2-8690-722a1b84a6c9 (old id 1223667)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18667612?dopt=Abstract
date added to LUP
2008-09-02 09:00:02
date last changed
2017-05-14 04:30:03
@article{81e64a98-bb71-41f2-8690-722a1b84a6c9,
  abstract     = {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.},
  author       = {Wisman, Liselijn and Sahin, Gurdal and Maingay, Matthew and Leanza, Giampiero and Kirik, Deniz},
  issn         = {1529-2401},
  keyword      = {Nerve Degeneration: physiopathology,Memory: physiology,Maze Learning: physiology,Hippocampus: physiology,Cholinergic Fibers: physiology,Dopamine: physiology,Neural Pathways: physiology},
  language     = {eng},
  number       = {31},
  pages        = {7797--7807},
  publisher    = {Society for Neuroscience},
  series       = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
  title        = {Functional convergence of dopaminergic and cholinergic input is critical for hippocampus-dependent working memory.},
  url          = {http://dx.doi.org/10.1523/JNEUROSCI.1885-08.2008},
  volume       = {28},
  year         = {2008},
}