Inactivation mode of sodium channels defines the different maximal firing rates of conventional versus atypical midbrain dopamine neurons
Fig 8
Response of midbrain dopamine cells with identified projection targets to additional depolarization after inducing depolarization block with a current step.
A1, B1. Double labeling of cells with TH (tyrosine hydroxylase) to confirm dopaminergic phenotype and retrobeads (RB) to confirm projection target is medial shell (A1) or lateral shell (B2). A2, B2. Rebound response of identified cells to 2s of hyperpolarizing current. Cell from A1 does not show significant sag potential and has a 1.9 s rebound delay, confirming atypical phenotype (A2). Cell from B1 has a post sag potential of +19 mV and a rebound delay of 145 ms, consistent with conventional phenotype (B2). A3. Action potential waveform during pacing of identified medial shell projecting cell from A1. Action potential threshold is -30 mV and width at threshold is 5.2 ms. A4. Phase plot (slope vs voltage) of action potential in A3. Peak slopes are +30 and -18 V/s. B3. Action potential waveform during pacing of identified lateral shell projecting cell from B1. Action potential threshold is -27 mV and width at threshold is 3.7 ms. B4. Phase plot of action potential in B3. Peak slopes are +70 and -33 V/s. A5. Voltage trace of entry into depolarization block in response to 2s 125 pA pulse with an additional 200 ms pulse of 75 pA after 1.5 s for medial projecting cell identified in A1. Spike amplitude decays continuously into near threshold oscillation with a peak frequency (avg of first 3 ISI) is 40.5 Hz and a terminal frequency (average of final 3 ISI) of 20.7 Hz. Additional current pulse evokes a 20 mV amplitude oscillation. A6. Plot of dV/dt for voltage trace in A5. Slope declines continuously to below 5 V/s spike threshold. Peak slope of evoked oscillation is 2.6 V/s. B5. Voltage vs time in response to 2s 300 pA pulse with additional 200 ms pulse of 75 pA after 1.5 s in lateral projecting cell identified in B1. Spike amplitude remains consistent with a peak frequency of 15.7 hz and terminal frequency of 8.7 Hz. Additional current pulse evokes a 44 mV amplitude spike. B6. Plot of dV/dt for voltage trace in B5. Slope declines from spike to spike with final spike having a peak amplitude of 25 V/s. Evoked spike has a peak slope of 18 V/s, well above spike threshold of 5 V/s.