Figure 1: Ghrelin increases excitability of dopaminergic neurons in substantia nigra.

(a) Dentification of dopaminergic neurons in SNc. Left panel shows recording of a putative dopaminergic neuron characterized by large cell body (26 μm) and triangular multipolar shape under Differential Interference Contrast microscope. Middle panel: dopaminergic neurons were further identified by the presence of a large sag (arrow) in the voltage response to hyperpolarizing current steps. The example neuron fired regular spikes in response to 50 pA injection. Below shows the current steps from −100 pA with 50-pA increments. Right panel: the expanded view of an action potential showing the half width of 3 ms. (b) Representative raw traces of spontaneous action potentials were recorded before, during, and after application of ghrelin (10 nM, n=43). A concentration of 10 nM ghrelin reversibly increased the firing frequency from 1.2 Hz to 1.5 Hz for the example neuron. (c) High concentration of ghrelin (100 nM) changed the neuronal discharge pattern from pacemaker mode to burst firing. (d) Dose–response curve for ghrelin in which firing rate is plotted against ghrelin concentrations from 0.1 to 1,000 nM (n=6–9). Data were fitted to a sigmoid dose–response function with half maximal effective concentration (EC₅₀) of 12.3 nM. Each bar represents the mean±s.e.m. Scale bar, (left), 20 μm (a).