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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Main Authors: Katie A. Jennings, Nicola J. Platt, Stephanie J. Cragg
Format: Article
Language:English
Published: Elsevier 2015-10-01
Series:Neurobiology of Disease
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996115002338
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spelling 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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