Fig. 6: αSyn PFF deposition impairs the resilience of SNc dopamine neurons to hyperpolarization challenge.

A Experimental design: Four weeks post unilateral αSyn PFF deposition (2 µg/µL; 1µL per hemisphere; 0.5µL in the SNc and 0.5µL in the VTA), the 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 s. After returning to resting membrane potential, post-stress firing frequency was measured to assess resilience. B, C Representative electrophysiological traces from SNc dopamine neurons before and after the 30-second hyperpolarization step. F The corresponding graph quantifies the percentage change in firing frequency, showing a reduced capacity of SNc neurons to recover following hyperpolarization stress when exposed to αSyn PFF. (D, E) Representative traces from VTA dopamine neurons at baseline and post-hyperpolarization. G The associated graph indicates that VTA neurons maintain stable firing frequencies and remain unaffected by PFF deposition under these conditions. Error bars represent mean ± SEM. Data were obtained from  4–6 mice, resulting in a sample size of n = 6 - 22 neurons. Statistical significance was determined by t-test (**p < 0.01).