Excitatory nicotinic signaling drives action potential bursting in dopaminergic axons

Axons of dopamine (DA) neurons express nicotinic receptors (nAChRs) that have been shown to both facilitate and suppress striatal DA release, but the mechanisms underlying these opposing actions are unclear. We combined axonal recordings and calcium imaging approaches to examine the effects of nAChRs on DAergic axon excitability. Activation of nAChRs consistently depolarized DAergic axons and increased the probability of evoking action potentials. Calcium imaging experiments showed that weak or moderate stimulation of striatal cholinergic interneurons (CINs) activated DAergic axons, while strong stimulation blunted multi-pulse protocols. Axon recordings showed that highly synchronous stimulation of CINs triggered a rapid (~125 Hz) burst of 2-4 action potentials in DAergic axons. Imaging experiments showed that nAChR-evoked axon bursts led to prolonged refractoriness, which was mimicked by direct burst stimulation. Thus, nAChR activation locally enhances excitability of DAergic axons over a range of intensities, including the production of locally generated burst firing and subsequent refractory inhibition.