BMedSc(Hon) abstracts 2024

BackgroundCompared to the motor symptoms of Basal Ganglia diseases, like Parkinson's, the less easily recognised non-motor symptoms have more poorly characterised pathophysiologies.Because the substantia-nigra-pars-lateralis (SNl) specifically terminates in the tail-striatum (TS), which receives sensory information, its dysfunction likely contributes to non-motor symptoms.The main target of deep brain stimulation (DBS) used in Parkinson's treatment is the subthalamic-nucleus (STN).We have recently shown this to regulate dopamine release in the TS by directly modulating SNl firing.Little is known about this pathway.The firing patterns of rat SNl dopamine-neurons were characterised using electrophysiological techniques to better understand the non-motor basal ganglia pathways. Materials and MethodsIn vivo insertion in rats (urethane anaesthetised) of a bipolar-electrode into STN and multielectrode-array into SNl.Neurons were identified from depth, spontaneous firing frequency and action potential shape/duration.STN stimulated with DBS-like parameters (1mA, 10-150Hz, 0.1ms-pulse, 2s-train) and output recorded with OpenEphys-electrophysiology-platform.Characterisation algorithms programmed in MATLAB. Results130Hz stimulation raised SNl firing frequency 2.2 0.4x above its 8.5 4.5Hz baseline (no effect < 60Hz).Numerous parameters, including basal frequency with its coefficient-of-variation, and following STN-stimulation, peak firing frequency and timing of response were characterised.Only frequency and shape combined distinguished individual neurons. ConclusionSNl firing patterns show distinctive characteristics from other substantia-nigra neurons.Only high-frequency STN stimulation excited SNl dopamine-neurons, consistent with only high frequency DBS treatment of Parkinson's being effective.This possibly indicates a dopamine-neuron excitation mechanism for DBS.Understanding SNl dopamine-neuron firing patterns helps elucidate non-motor symptom pathogenesis, previously often unrecognised or viewed as untreatable.