Imaging striatal dopamine release using a nongenetically encoded near infrared fluorescent catecholamine nanosensor

Area of Science:

• Neuroscience
• Biomedical Engineering
• Chemical Sensing

Background:

• Neuromodulation is crucial for brain function and implicated in various neurological diseases.
• Existing tools lack the required spatial and temporal resolution to fully capture neuromodulatory dynamics.
• Development of advanced biosensors is essential for understanding complex brain circuitry.

Purpose of the Study:

• To introduce a novel synthetic catecholamine nanosensor for neuromodulation studies.
• To evaluate the nanosensor's capability in measuring dopamine release in brain tissue.
• To assess the nanosensor's compatibility with pharmacological interventions and its utility in studying receptor modulation.

Main Methods:

• Development of a synthetic catecholamine nanosensor with near-infrared fluorescence (1000-1300 nm), termed nIRCat.
• Measurement of electrically and optogenetically evoked dopamine release in brain tissue using nIRCats.
• Assessment of nIRCat compatibility with dopamine pharmacology and investigation of D2 autoreceptor modulation.

Main Results:

• nIRCats successfully measured dopamine release in brain tissue with high spatial resolution, identifying hotspots as small as 2 µm.
• The nanosensor demonstrated compatibility with established dopamine pharmacology.
• D2 autoreceptor modulation of dopamine release was observed, varying with initial release magnitude at different hotspots.

Conclusions:

• nIRCats represent a versatile synthetic optical tool for monitoring neuromodulatory neurotransmitter release.
• The nanosensor enables high-resolution mapping of dopamine release dynamics in the brain.
• This technology facilitates a deeper understanding of neuromodulation in both healthy and diseased states.