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Rapid signalling in distinct dopaminergic axons during locomotion and reward

2016; Nature Portfolio; Volume: 535; Issue: 7613 Linguagem: Inglês

10.1038/nature18942

1476-4687

Mark W. Howe, Daniel A. Dombeck,

Neurological disorders and treatments

Fast phasic signals in dopaminergic axons in the dorsal striatum occur during, and can induce, motor accelerations in mice, and these signals are transmitted by a largely distinct population of dopaminergic axons from those that signal reward. In one important model of striatum-targeting dopamine neurons, phasic dopamine release is assumed to drive reward-based learning, whereas tonic dopamine release biases the system towards or away from movement. Mark Howe and Daniel Dombeck now show that fast phasic signals in dopaminergic axons in the dorsal striatum occur during — and can induce — motor accelerations in mice. They further show that locomotion-signalling axons originate in the substantia nigra pars compacta and mainly target the dorsal striatum, whereas reward-signalling axons originate in the ventral tegmental area and mainly target the ventral striatum. These findings show that dopamine signals can influence both reward learning and movement with sub-second precision, and suggest that both precise signal timing and neuronal subtype are relevant to the treatment of dopamine-related disorders. Dopaminergic projection axons from the midbrain to the striatum are crucial for motor control, as their degeneration in Parkinson disease results in profound movement deficits. Paradoxically, most recording methods report rapid phasic dopamine signalling (~100-ms bursts) in response to unpredicted rewards, with little evidence for movement-related signalling. The leading model posits that phasic signalling in striatum-targeting dopamine neurons drives reward-based learning, whereas slow variations in firing (tens of seconds to minutes) in these same neurons bias animals towards or away from movement. However, current methods have provided little evidence to support or refute this model. Here, using new optical recording methods, we report the discovery of rapid phasic signalling in striatum-targeting dopaminergic axons that is associated with, and capable of triggering, locomotion in mice. Axons expressing these signals were largely distinct from those that responded to unexpected rewards. These results suggest that dopaminergic neuromodulation can differentially impact motor control and reward learning with sub-second precision, and indicate that both precise signal timing and neuronal subtype are important parameters to consider in the treatment of dopamine-related disorders.