Electrical and Ca(2+) signaling in dendritic spines of substantia nigra dopaminergic neurons

Little is known about the density and function of dendritic spines on midbrain dopamine neurons, or the relative contribution of spine and shaft synapses to excitability. Using Ca(2+) imaging, glutamate uncaging, fluorescence recovery after photobleaching and transgenic mice expressing labeled PSD-95, we comparatively analyzed electrical and Ca(2+) signaling in spines and shaft synapses of dopamine neurons. Dendritic spines were present on dopaminergic neurons at low densities in live and fixed tissue. Uncaging-evoked potential amplitudes correlated inversely with spine length but positively with the presence of PSD-95. Spine Ca(2+) signals were less sensitive to hyperpolarization than shaft synapses, suggesting amplification of spine head voltages. Lastly, activating spines during pacemaking, we observed an unexpected enhancement of spine Ca(2+) midway throughout the spike cycle, likely involving recruitment of NMDA receptors and voltage-gated conductances. These results demonstrate functionality of spines in dopamine neurons and reveal a novel modulation of spine Ca(2+) signaling during pacemaking. DOI: http://dx.doi.org/10.7554/eLife.13905.001