The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation

Abstract 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 contributin...

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Bibliographic Details
Published in:Neurobiology of disease 2015-10, Vol.82, p.262-268
Main Authors: Jennings, Katie A, Platt, Nicola J, Cragg, Stephanie J
Format: Article
Language:English
Subjects:
6-OHDA
Acetylcholine
Animals
Cocaine - pharmacology
Corpus Striatum - drug effects
Corpus Striatum - metabolism
Dopamine
Dopamine - metabolism
Dopamine Uptake Inhibitors - pharmacology
Fast-scan cyclic voltammetry
Male
Mice, Inbred C57BL
Neurology
Nicotinic receptors
Oxidopamine
Parkinsonian
Parkinsonian Disorders - metabolism
Phasic dopamine
Presynaptic Terminals - drug effects
Presynaptic Terminals - metabolism
Receptors, Nicotinic - metabolism
Release probability
Striatum
Synaptic Transmission - drug effects
Synaptic Transmission - physiology
Tissue Culture Techniques
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Summary:Abstract 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.
ISSN:0969-9961
1095-953X
DOI:10.1016/j.nbd.2015.06.015