The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation
Dopamine function is disturbed in Parkinson's disease (PD), but whether and how release of dopamine from surviving neurons is altered has long been debated. Nicotinic acetylcholine receptors (nAChRs) on dopamine axons powerfully govern dopamine release and could be critical contributing factors...
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doaj-bcae94cde384400aaa3046efc02857ab2021-03-22T12:43:10ZengElsevierNeurobiology of Disease1095-953X2015-10-0182262268The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activationKatie A. Jennings0Nicola J. Platt1Stephanie J. Cragg2Corresponding author at: Department of Physiology, Anatomy & Genetics, Sherrington Building, Parks Road, Oxford OX1 3PT, UK.; Department of Physiology, Anatomy Genetics, Oxford Parkinson's Disease Centre, Parks Road, Oxford OX1 3PT, UKDepartment of Physiology, Anatomy Genetics, Oxford Parkinson's Disease Centre, Parks Road, Oxford OX1 3PT, UKDepartment of Physiology, Anatomy Genetics, Oxford Parkinson's Disease Centre, Parks Road, Oxford OX1 3PT, UKDopamine function is disturbed in Parkinson's disease (PD), but whether and how release of dopamine from surviving neurons is altered has long been debated. Nicotinic acetylcholine receptors (nAChRs) on dopamine axons powerfully govern dopamine release and could be critical contributing factors. We revisited whether fundamental properties of dopamine transmission are changed in a parkinsonian brain and tested the potentially profound masking effects of nAChRs. Using real-time detection of dopamine in mouse striatum after a partial 6-hydroxydopamine lesion and under nAChR inhibition, we reveal that dopamine signals show diminished sensitivity to presynaptic activity. This effect manifested as diminished contrast between DA release evoked by the lowest versus highest frequencies. This reduced activity-dependence was underpinned by loss of short-term facilitation of dopamine release, consistent with an increase in release probability (Pr). With nAChRs active, the reduced activity-dependence of dopamine release after a parkinsonian lesion was masked. Consequently, moment-by-moment variation in activity of nAChRs may lead to dynamic co-variation in dopamine signal impairments in PD.http://www.sciencedirect.com/science/article/pii/S0969996115002338ParkinsonianDopamineAcetylcholineNicotinic receptorsPhasic dopamine6-OHDA |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Katie A. Jennings Nicola J. Platt Stephanie J. Cragg |
spellingShingle |
Katie A. Jennings Nicola J. Platt Stephanie J. Cragg The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation Neurobiology of Disease Parkinsonian Dopamine Acetylcholine Nicotinic receptors Phasic dopamine 6-OHDA |
author_facet |
Katie A. Jennings Nicola J. Platt Stephanie J. Cragg |
author_sort |
Katie A. Jennings |
title |
The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation |
title_short |
The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation |
title_full |
The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation |
title_fullStr |
The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation |
title_full_unstemmed |
The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation |
title_sort |
impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2015-10-01 |
description |
Dopamine function is disturbed in Parkinson's disease (PD), but whether and how release of dopamine from surviving neurons is altered has long been debated. Nicotinic acetylcholine receptors (nAChRs) on dopamine axons powerfully govern dopamine release and could be critical contributing factors. We revisited whether fundamental properties of dopamine transmission are changed in a parkinsonian brain and tested the potentially profound masking effects of nAChRs. Using real-time detection of dopamine in mouse striatum after a partial 6-hydroxydopamine lesion and under nAChR inhibition, we reveal that dopamine signals show diminished sensitivity to presynaptic activity. This effect manifested as diminished contrast between DA release evoked by the lowest versus highest frequencies. This reduced activity-dependence was underpinned by loss of short-term facilitation of dopamine release, consistent with an increase in release probability (Pr). With nAChRs active, the reduced activity-dependence of dopamine release after a parkinsonian lesion was masked. Consequently, moment-by-moment variation in activity of nAChRs may lead to dynamic co-variation in dopamine signal impairments in PD. |
topic |
Parkinsonian Dopamine Acetylcholine Nicotinic receptors Phasic dopamine 6-OHDA |
url |
http://www.sciencedirect.com/science/article/pii/S0969996115002338 |
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