Calcium-activated SK channels control firing regularity by modulating sodium channel availability in midbrain dopamine neurons

作者: Rajeshwari Iyer , Mark A. Ungless , Aldo A. Faisal

DOI: 10.1038/S41598-017-05578-5

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摘要: Dopamine neurons in the substantia nigra pars compacta and ventral tegmental area regulate behaviours such as reward-related learning, motor control. Dysfunction of these is implicated Schizophrenia, addiction to drugs, Parkinson’s disease. While some dopamine fire single spikes at regular intervals, others irregular interspersed with bursts. Pharmacological inhibition calcium-activated potassium (SK) channels increases variability their firing pattern, sometimes also increasing number fired bursts, indicating that SK play an important role maintaining neuron regularity burst firing. However, exact mechanisms underlying effects are still unclear. Here, we develop a biophysical model incorporating ion channel stochasticity enabled analysis availability multiple states during spiking. We find decreased primarily due significant decrease AHP turn resulted reduction fraction available voltage-gated sodium insufficient recovery from inactivation. Our further predicts results depolarisation action potential threshold along increase its variability.

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