Dopamine - induced oscillations of the pyloric 2 pacemaker neuron rely on release of calcium from 3 intracellular stores

31 Endogenously bursting neurons play central roles in many aspects of 32 nervous system function, ranging from motor control to perception. The 33 properties and bursting patterns generated by these neurons are subject to 34 neuromodulation, which can alter cycle frequency and amplitude by 35 modifying the properties of the neuron’s ionic currents. In the 36 stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus, 37 the Anterior Burster (AB) neuron is a conditional oscillator in the 38 presence of dopamine (DA) and other neuromodulators, and serves as the 39 pacemaker to drive rhythmic output from the pyloric network. We 40 analyzed the mechanisms by which DA evokes bursting in the AB neuron. 41 Previous work showed that DA-evoked bursting is critically dependent on 42 external calcium (Harris-Warrick and Flamm,1987). Using two-photon 43 microscopy and calcium imaging, we show that DA evokes the release of 44 calcium from intracellular stores well before the emergence of voltage 45 oscillations. When this release from intracellular stores is blocked by 46 antagonists of Ryanodineor IP3receptor-channels, DA fails to evoke 47 AB bursting. We further demonstrate that DA enhances the calcium48 activated inward current, ICAN, despite the fact that it significantly reduces 49 voltage-activated calcium currents. This suggests that DA–induced release 50 of calcium from intracellular stores activates ICAN, which provides a 51 depolarizing ramp current that underlies endogenous bursting in the AB 52