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:
https://lup.lub.lu.se/record/1223667
- author
- Wisman, Liselijn
LU
; Sahin, Gurdal
LU
; Maingay, Matthew
LU
; Leanza, Giampiero
LU
and Kirik, Deniz
LU
- organization
- publishing date
- 2008
- 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
- pmid:18667612
- 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
- 2016-04-04 09:44:24
- date last changed
- 2023-09-06 03:32:30
@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}},
keywords = {{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}},
doi = {{10.1523/JNEUROSCI.1885-08.2008}},
volume = {{28}},
year = {{2008}},
}