Fig. 5: hαSyn overexpression compromises the resilience of SNc dopamine neurons to hyperpolarization challenge.
From: Parkinson’s paradox: alpha-synuclein’s selective strike on SNc dopamine neurons over VTA

A Experimental design: Four weeks after unilateral hαSyn injection (1 µL), basal firing frequency of SNc dopamine neurons was recorded both ipsilaterally (injected side; inj) and contralaterally (non-injected side; no-inj). Neurons were then hyperpolarized to –100 mV for 30 second. Following restoration of the resting membrane potential, post stress firing frequency was assessed to determine resilience to hyperpolarization. B, C Representative electrophysiological traces from SNc dopamine neurons before and after the 30-second hyperpolarization step. F The accompanying graph shows the percentage change in firing frequency, revealing a diminished capacity of SNc neurons to recover following hyperpolarization stress in the presence of hαSyn. D, E Representative traces from VTA dopamine neurons at baseline and post-hyperpolarization. G The associated graph demonstrates that VTA neurons effectively buffer the hyperpolarization-induced perturbation, maintaining firing rates without significant changes after hαSyn overexpression. Error bars represent mean ± SEM. Data was obtained from 3-4 mice, with a sample size of n = 4 - 13 neurons. Statistical significance was assessed by t-test (*p < 0.05).