SK- and h-current contribute to the generation of theta-like resonance of rat substantia nigra pars compacta dopaminergic neurons at hyperpolarized membrane potentials

摘要

Oscillation activities are the feature of neural network and correlated to different physiological states. The theta (θ) oscillation (2–7 Hz) has been reported in the basal ganglia, and the intrinsic resonance properties of individual neurons have provided a basis for this network oscillation. The basal ganglia neurons receive comprehensive modulation arising from dopaminergic (DA) neurons located in the substantia nigra pars compacta (SNc), but how the oscillation is regulated in SNc DA neurons remains poorly understood. In this paper, whole-cell patch-clamp recordings were performed on SNc DA neurons in rat brain slices to reveal the resonance properties and underlying mechanisms. After swept-sine-wave (ZAP protocol) current was injected into SNc DA neurons, θ resonance was induced, whose peak impedance went up with the rising of temperature, demonstrating the dependency of resonance on temperature. Voltage dependency of resonance was also observed at hyperpolarized membrane potentials. Further investigation demonstrated two individual components: (1) SK-current generated resonance at around −65 mV, which could be blocked by apamin (300 nM), a specific antagonist of the small-conductance calcium-dependent potassium channel; (2) h-current (I _h) generated resonance at around −75 mV, which could be abolished by ZD7288 (10 μM), a selective blocker of HCN channels. We concluded that in SNc DA neurons, θ resonance was mediated by two distinct ionic channels at hyperpolarized potentials. Our results imply that θ frequency resonance of individual SNc DA neurons may participate in coordinating rhythmic firing activity and contribute to the physiological or pathophysiological behaviors of Parkinson’s disease.