Evoked transients of pH-sensitive fluorescent false neurotransmitter reveal dopamine hot spots in the globus pallidus
- Columbia University, United States
Abstract
Dopamine neurotransmission is suspected to play important physiological roles in multiple sparsely innervated brain nuclei, but there has not been a means to measure synaptic dopamine release in such regions. The globus pallidus externa (GPe) is a major locus in the basal ganglia that displays a sparse innervation of en passant dopamine axonal fibers. Due to the low levels of innervation that preclude electrochemical analysis, it is unknown if these axons engage in neurotransmission. To address this, we introduce an optical approach using a pH-sensitive fluorescent false neurotransmitter, FFN102, that exhibits increased fluorescence upon exocytosis from the acidic synaptic vesicle to the neutral extracellular milieu. In marked contrast to the striatum, FFN102 transients in the mouse GPe were spatially heterogeneous, smaller than in striatum with the exception of sparse hot spots, and significantly enhanced by high frequency stimulation. Our results support hot spots of dopamine release from substantia nigra axons.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Christoph Kellendonk
Funding
NIH Office of the Director (R01 NS101982)
- Un Jung Kang
- David Sulzer
U.S. Department of Defense (PR161817)
- Un Jung Kang
Parkinson's Disease Foundation
- Timothy Cheung
- Un Jung Kang
- David Sulzer
NARSAD
- Christoph Kellendonk
JPB Foundation
- David Sulzer
NIH Office of the Director (R01 DA07418)
- David Sulzer
NIH Office of the Director (R03 NS096494)
- Un Jung Kang
NIH Office of the Director (RO1 MH093672)
- Christoph Kellendonk
NIH Office of the Director (T32 NS06492B-04)
- Jozsef Meszaros
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal protocols followed NIH guidelines and were approved by Columbia University's Institutional Animal Care and Use Committee.
Copyright
© 2018, Meszaros et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Evoked transients of pH-sensitive fluorescent false neurotransmitter reveal dopamine hot spots in the globus pallidus
eLife 7:e42383.
https://doi.org/10.7554/eLife.42383
