Triple-color fiber photometry recording of dopamine, glutamate and striatal neural activity

Authors

• KR LeFort
• B Ray
• W Rungratanawanich
• BJ Song

Abstract

The striatum is the largest nucleus and the hub of the basal ganglia that integrates glutamatergic inputs from the cortex and the thalamus, and dopaminergic input from the substantia nigra pars compacta. It has been hypothesized that glutamate is the main driving force to excite striatal neurons and that dopamine differentially regulates the activities of striatonigral and striatopallidal spiny projection neurons (SPNs). To directly test this hypothesis, we used spectrally resolved fiber photometry and genetically encoded fluorescent indicators GRAB-DA2m (green), iGluSnFR3 (yellow) and jRGECO1a (red) to simultaneously measure the striatal dopamine and glutamate release and the neural activities of striatonigral or striatopallidal SPNs in D1-Cre or A2A-Cre mice. We show that the closely overlapped fluorescence emission spectra of GRAB-DA2m and iGluSnFR3 can be acutely extracted from the recorded spectra by linear spectral unmixing. These results show that spectral unmixing using spectrally resolved fiber photometry is a powerful tool to investigate the interactions between multiple elements in a brain circuit.

Scientific Focus Area: Neuroscience

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