Evoked transients of pH-sensitive fluorescent false neurotransmitter reveal dopamine hot spots in the globus pallidus
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 and smaller than in striatum with the exception of sparse hot spots. GPe transients were also significantly enhanced by high frequency stimulation. Our results support hot spots of dopamine release from substantia nigra axons.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 19, 2018
- Source ID
- 10.7554/elife.42383
Entities
People
- Christoph Kellendonk
- Dalibor Sames
- David Sulzer
- Jozsef Meszaros
- Maya M Erler
- Timothy Cheung
- Un Jung Kang
Organizations
- Columbia University
- Freedom Together Foundation
- National Institute of Mental Health
- National Institute of Neurological Disorders and Stroke
- National Institute on Drug Abuse
- National Institutes of Health
- Parkinson's Foundation
- United States Department of Defense