Laboratory for Functional Optical Imaging, Department of Biomedical Engineering, Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, United States; Graduate Program in Neurobiology and Behavior, Columbia University, New York, United States
Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, United States; Department of Psychiatry, Columbia University, New York, United States; Department of Pharmacology, Columbia University, New York, United States
Department of Neurology, Columbia University, New York, United States; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, United States; Department of Psychiatry, Columbia University, New York, United States; Department of Pharmacology, Columbia University, New York, United States
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.
