Emotional memory impairments induced by AAV-mediated overexpression of human α-synuclein in dopaminergic neurons of the ventral tegmental area.
Alvarsson, A ; Caudal, D ; Björklund, Anders LU
and Svenningsson, P
(2016)
In Behavioural Brain Research
296.
p.129-133
- Abstract
- Parkinson's disease (PD) is associated with extensive degeneration of dopaminergic neurons originating in the substantia nigra pars compacta, but neuronal loss is also found in the ventral tegmental area (VTA). The VTA projects to areas involved in cognitive and emotional processes, including hippocampus, amygdala, nucleus accumbens and prefrontal cortex, and has thus been proposed to play a role in emotional memory impairments in PD. Since the formation of α-synuclein inclusions throughout the central nervous system is a pathological hallmark of PD, we studied the progressive effects of α-synuclein overexpression in the VTA on motor functions, emotional behaviour and emotional memory. Adeno-associated viral (AAV) vectors encoding either... (More)
- Parkinson's disease (PD) is associated with extensive degeneration of dopaminergic neurons originating in the substantia nigra pars compacta, but neuronal loss is also found in the ventral tegmental area (VTA). The VTA projects to areas involved in cognitive and emotional processes, including hippocampus, amygdala, nucleus accumbens and prefrontal cortex, and has thus been proposed to play a role in emotional memory impairments in PD. Since the formation of α-synuclein inclusions throughout the central nervous system is a pathological hallmark of PD, we studied the progressive effects of α-synuclein overexpression in the VTA on motor functions, emotional behaviour and emotional memory. Adeno-associated viral (AAV) vectors encoding either human α-synuclein or green fluorescent protein (GFP) were injected stereotactically into the VTA, and behaviour was monitored 3 and 8 weeks following AAV injection. At week 8, there was a 22% reduction of TH+ neurons in the VTA. We demonstrate that α-synuclein overexpression in dopaminergic neurons of the VTA induced mild motor deficits that appeared 3 weeks following AAV-α-synuclein injection and were aggravated at week 8. No depressive- or anxiety-like behaviours were found. To address emotional memory, we used the passive avoidance test, a one-trial associative learning paradigm based on contextual conditioning which requires minimal training. Interestingly, emotional memory impairments were found in α-synuclein overexpressing animals at week 8. These findings indicate that α-synuclein overexpression induces progressive memory impairments likely caused by a loss of function of mesolimbic dopaminergic projections. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8043197
- author
- Alvarsson, A
; Caudal, D
; Björklund, Anders
LU
and Svenningsson, P
- organization
- publishing date
- 2016
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Behavioural Brain Research
- volume
- 296
- pages
- 129 - 133
- publisher
- Elsevier
- external identifiers
-
- pmid:26341317
- wos:000366079100018
- scopus:84941985397
- pmid:26341317
- ISSN
- 0166-4328
- DOI
- 10.1016/j.bbr.2015.08.034
- language
- English
- LU publication?
- yes
- id
- c1145f65-5efc-4059-877e-115113962b1a (old id 8043197)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26341317?dopt=Abstract
- date added to LUP
- 2016-04-01 10:26:04
- date last changed
- 2022-05-13 08:50:14
@article{c1145f65-5efc-4059-877e-115113962b1a,
abstract = {{Parkinson's disease (PD) is associated with extensive degeneration of dopaminergic neurons originating in the substantia nigra pars compacta, but neuronal loss is also found in the ventral tegmental area (VTA). The VTA projects to areas involved in cognitive and emotional processes, including hippocampus, amygdala, nucleus accumbens and prefrontal cortex, and has thus been proposed to play a role in emotional memory impairments in PD. Since the formation of α-synuclein inclusions throughout the central nervous system is a pathological hallmark of PD, we studied the progressive effects of α-synuclein overexpression in the VTA on motor functions, emotional behaviour and emotional memory. Adeno-associated viral (AAV) vectors encoding either human α-synuclein or green fluorescent protein (GFP) were injected stereotactically into the VTA, and behaviour was monitored 3 and 8 weeks following AAV injection. At week 8, there was a 22% reduction of TH+ neurons in the VTA. We demonstrate that α-synuclein overexpression in dopaminergic neurons of the VTA induced mild motor deficits that appeared 3 weeks following AAV-α-synuclein injection and were aggravated at week 8. No depressive- or anxiety-like behaviours were found. To address emotional memory, we used the passive avoidance test, a one-trial associative learning paradigm based on contextual conditioning which requires minimal training. Interestingly, emotional memory impairments were found in α-synuclein overexpressing animals at week 8. These findings indicate that α-synuclein overexpression induces progressive memory impairments likely caused by a loss of function of mesolimbic dopaminergic projections.}},
author = {{Alvarsson, A and Caudal, D and Björklund, Anders and Svenningsson, P}},
issn = {{0166-4328}},
language = {{eng}},
pages = {{129--133}},
publisher = {{Elsevier}},
series = {{Behavioural Brain Research}},
title = {{Emotional memory impairments induced by AAV-mediated overexpression of human α-synuclein in dopaminergic neurons of the ventral tegmental area.}},
url = {{http://dx.doi.org/10.1016/j.bbr.2015.08.034}},
doi = {{10.1016/j.bbr.2015.08.034}},
volume = {{296}},
year = {{2016}},
}