Fiber photometry of SNc/SNr dopamine and GABA neuron responses to optogenetic STN and PPN stimulation in Parkinson's disease

This dataset contains fiber photometry recordings examining differential responses of Parkinson's disease (PD)-vulnerable and -resilient dopamine neuron subtypes to excitatory input in freely-moving mice. The study investigates how excitatory inputs from the subthalamic nucleus (STN) and pedunculopontine nucleus (PPN) differentially modulate distinct dopaminergic and GABAergic populations in the substantia nigra (SNc/SNr) and their striatal projections. Using genetically-targeted calcium imaging with GCaMP6f/8f indicators and GRAB_DA sensors, the dataset captures activity across five experimental groups: (1) SNr GABAergic neurons, (2) SNc pan-dopaminergic neurons, (3) Parkinson's-vulnerable Anxa1+ and -resilient Vglut2+ dopamine subtypes, (4) striatal dopamine release in dorsolateral and tail striatum, and (5) dopaminergic axon terminals. ChrimsonR-mediated optogenetic stimulation (635nm, 5mW) was delivered to STN and/or PPN at varying frequencies (5, 10, 20, 40 Hz) and durations (250ms, 1s, 4s) to probe circuit-specific responses. Key findings demonstrate that excitatory inputs evoke frequency-dependent excitation in SNr GABA neurons but heterogeneous, multiphasic responses in dopamine populations. Critically, PD-resilient Vglut2+ dopamine neurons show excitatory responses to STN/PPN input, while vulnerable Anxa1+ neurons are inhibited, revealing opposite functional properties between these subtypes. Striatal recordings show differential regional responses, with increased dopamine release in caudal striatum but inhibition followed by rebound in dorsolateral striatum. Each session includes raw and processed fiber photometry signals (demodulated calcium/isosbestic traces, downsampled signals, and DF/F), precisely-timed optogenetic stimulation epochs, and behavioral videos where available.