A dLight-ful New View of Neuromodulation

Abstract

Neuromodulators such as dopamine can transform neural circuit function, but the mechanisms underlying such transformations are incompletely understood. A recent study introduced dLight1, a genetically encoded fluorescent dopamine indicator. dLight1 allows the optical measurement of dopamine sensed by isolated target circuits with high spatiotemporal resolution and has unique advantages for the study of neuromodulatory mechanisms.

Keywords: dopamine; genetically encoded indicators; imaging; neuromodulation.

Figure 1.. Compatibility of dLight1 with existing optical technologies

A) DLight1 was created by replacing the third intracellular loop on a human dopamine receptor with a circularly permuted green fluorescent protein (cpGFP) module. When dopamine (DA) is released by a nearby presynaptic terminal, it binds to dLight1, causing an increase in fluorescence of cpGFP. B) An example of in vivo 2-photon dLight1 imaging in cortex through a cranial window. The heatmap shows the pattern of dLight1.2 expression. Boxes show computationally defined regions-of-interest (ROIs) for analysis. Coloring of the ROIs indicates the associated activity observed during behavior (reward signaling, locomotion, or non-significant). C)An example of dual-color fiber photometry in nucleus accumbens using dLight1.1 paired with the red calcium indicator jRGECO1a. When the mice are given unpredictable footshocks, dLight1 fluorescence decreases, whereas jRGECO1a fluorescence increases. D)An example of fiber photometry measurement of dLight1.1 signals in nucleus accumbens, paired with optogenetic stimulation of VTA dopamine neurons (which project to the nucleus accumbens) using the red-shifted excitatory opsin ChrimsonR. Stimulation of dopaminergic inputs to the nucleus accumbens leads to a frequency-dependent increase in dLight1 fluorescence. No increase in fluorescence is seen using the dLight1 control sensor. Figure panels B-D from Patriarchi et al. [1]. Reprinted with permission from AAAS.