Saturday, April 4, 2020

Dopaminergic neurons from the VTA and SNc control movement reinforcement

The work presented in this manuscript aims to determine how dopaminergic midbrain neurons contribute to movement reinforcement and movement generation. To address this, the authors used in vivo optogenetics to activate halorhodopsin (eNpHR3.0) expressed in the ventral tegmental area (VTA), the region containing the cell body of mesolimbic dopaminergic neurons. They subjected mice to a Pavovian paradigm, in which they paired a conditioning olfactory cue with an unconditioned sweetened milk reward. After training, the olfactory cue triggered an anticipatory licking that began before reward delivery. Light inhibition of VTA neurons reduced this anticipatory licking (which occurs in the time window between cue presentation and reward delivery) more than consummatory licking (which occurs after reward delivery) and this effect scaled with reward size. Together, these results suggest that dopaminergic neurons control movement reinforcement more than generation. In subsequent experiments, they show that post-reward inhibition of dopaminergic neurons in the substantia nigra pars compacta (SNc) also inhibits anticipatory licking, suggesting that dopaminergic neurons in these two brain regions might have overlapping functions. Through a series of fiber photometry measures of GCaMP6f fluorescence, they showed that dopaminergic neurons are active both before and after reward delivery, with post-reward dopamine neuron activity regulating learning. These findings are important because they support the hypothesis that VTA and SNc neurons both contribute preferentially to movement reinforcement rather than generation, although they do not rule out the possibility that specific subsets of dopaminergic neurons may have specialized roles in controlling specific features of the movement execution process. 
Nikki Dolphin and Anna Tuttman


Reference
Lee K, Claar LD, Hachisuka A, Bakhurin KI, Nguyen J, Trott JM, Gill JL and Masmanidis SC (2020). Temporally restricted dopaminergic control of reward-conditioned movements. Nat Neurosci (23), 209–16.



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