Fig. 6

Agonist activation of D2R modulated the intrinsic firing properties of AST-derived dopamine neurons and mouse dopamine neurons overexpressing α-synuclein. In these neurons, bath application of quinpirole dispersed broadbrimmed burst firing to mixture of single spikes and small burst activity with an underlying “pacemaker-like” periodicity. a Left: interspike interval (ISI) distribution in AST-derived dopamine neurons. The 50% probability was below 0.25 s. Right: ISI distribution observed in AST-derived dopamine neurons after quinpirole application, the 50% probability was below 1 s. b Left: ISI distribution in mouse dopamine neurons overexpressing α-synuclein. Right: ISI distribution observed during quinpirole applications in mouse dopamine neurons overexpressing α-synuclein. c Left: Instantaneous frequency distribution in AST-derived dopamine neurons. Right: Instantaneous frequency distribution obtained from AST-derived dopamine neurons during quinpirole applications. d Left: instantaneous frequency distribution in mouse dopamine neurons overexpressing α-synuclein. Right: Instantaneous frequency distribution during quinpirole applications in mouse dopamine neurons overexpressing α-synuclein. e Mean firing frequency is plotted against %SWB of AST-derived DA neurons before (aqua blue) and during quinpirole applications (brown). Inset shows quinpirole reduces %SWB in both experimental groups. f Mean firing frequency is plotted against %SWB in mouse dopamine neurons overexpressing α-synuclein before (navy-blue) and during quinpirole applications (wine). g Mean firing frequency is plotted against up-state for AST-derived dopamine neurons before (aqua blue) and during quinpirole applications (brown). Inset shows quinpirole reduces the amplitude of up-state in both experimental groups. h Mean firing frequency is plotted against up-state for mouse dopamine neurons overexpressing α-synuclein before (navy-blue) and during quinpirole applications (wine). i and j Quinpirole application does not change the spike half-width or spike half-amplitude in either AST-derived dopamine neurons or mouse dopamine neurons overexpressing α-synuclein. k Interspike intervals are calculated over 1 min of spontaneous firing activity. Quinpirole application does not change the coefficients of variation of the interspike intervals in either AST-derived dopamine neurons or mouse dopamine neurons overexpressing α-synuclein. l, m and n Quinpirole decreases the spontaneous firing rates (l, baseline: 3.9 ± 0.8 Hz; quinpirole: 1.8 ± 0.5 Hz, n = 11, p < 0.05), %SWB (m, baseline: 95.1 ± 2%; quinpirole: 48.8 ± 4.9%, n = 11, p < 0.01) and up-state (n, baseline: 11.2 ± 0.7 mV; quinpirole: 5.4 ± 0.8 mV, n = 11, p < 0.01) in AST-derived dopamine neurons and in mouse dopamine neurons overexpressing α-synuclein (firing rates: baseline: 2.2 ± 0.1 Hz, quinpirole: 0.6 ± 0.2 Hz, p < 0.01; %SWB: baseline: 80.6 ± 5.5%; quinpirole: 48.2 ± 8.9% n = 12, p < 0.01; up-state: baseline: 10.8 ± 0.8 mV, quinpirole: 6.7 ± 1.0 mV, n = 12, p < 0.01). The experiments and analyses were performed in parallel and via a blinded experimental design