Dopamine Neuron Activity before Action Initiation

 

Nature volume 554, pages 244–248 (08 February 2018)

Dopamine neuron activity before action initiation gates and invigorates future movements

Joaquim Alves da Silva, et.al.

Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Lisbon, Portugal

Nova Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal

Neuropatologia molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico

Departments of Neuroscience and Neurology, Zuckerman Mind Brain Behavior Institute, Columbia University, New York, New York, USA

[paraphrase]

Deciding when and whether to move is critical for survival. Loss of dopamine neurons (DANs) of the substantia nigra pars compacta (SNc) in patients with Parkinson’s disease causes deficits in movement initiation and slowness of movement. The role of DANs in self-paced movement has mostly been attributed to their tonic activity, whereas phasic changes in DAN activity have been linked to reward prediction. This model has recently been challenged by studies showing transient changes in DAN activity before or during self-paced movement initiation. Nevertheless, the necessity of this activity for spontaneous movement initiation has not been demonstrated, nor has its relation to initiation versus ongoing movement been described. Here we show that a large proportion of SNc DANs, which did not overlap with reward-responsive DANs, transiently increased their activity before self-paced movement initiation in mice. This activity was not action-specific, and was related to the vigour of future movements. Inhibition of DANs when mice were immobile reduced the probability and vigour of future movements. Conversely, brief activation of DANs when mice were immobile increased the probability and vigour of future movements. Manipulations of dopamine activity after movement initiation did not affect ongoing movements. Similar findings were observed for the initiation and execution of learned action sequences. These findings causally implicate DAN activity before movement initiation in the probability and vigour of future movements.

Previous studies in patients with Parkinson’s disease and animal models have shown that dopamine depletion leads to less vigorous movements. We verified that overall, the activity of DANs 300 ms before movement initiation was significantly related to the vigour of future movements (measured by body acceleration. When doing per-trial analyses comparing all the lower vigour with the higher vigour initiations, we found that 38.5% of the neurons had significantly higher activity before higher vigour movements.

The results highlight a specific role for the transient activity of DANs for the gating and invigoration of self-paced movement initiation, but not for the modulation of ongoing movements.

These data suggest that different populations of SNc DANs are related to movement versus reward, but it remains to be determined whether these correspond to populations that project to the dorsal versus ventral striatum.

These results indicate that SNc dopamine activity before the initiation of the action sequence modulates the probability and latency of sequence initiation, but is not critical for the execution of ongoing sequences.

Our results indicate that the activity of DANs before movement onset modulates future movement vigour. This could explain why patients with Parkinson’s disease select less vigorous movements to initiate.  It is also in accordance with recent studies that have shown that activity of DAN terminals in the dorsal striatum preceded spontaneous movement initiation but did not precede and even followed acceleration bursts during ongoing movement7. Our results suggest that transient changes in dopamine can function as a fast system that acts on top of tonic release to increase the probability (and vigour) of initiating movements, presumably by modulating the excitability of striatal projection neurons, which receive information about the movements that are ‘planned’ at that exact time via glutamatergic inputs from cortex and/or thalamus. This suggests a role for dopamine in gating and invigorating movements that were planned elsewhere, and is consistent with the observation that DAN activity is not very action-specific. More sustained changes in DAN activity could represent states in which the ‘gate’ is more permissive, increasing the probability of action initiation during longer periods of time, therefore promoting movement. This would translate into more movement variability with exploration of the action space, which could be important in situations of uncertainty or learning.

These results highlight that approaches aimed at providing transient modulations of basal ganglia circuitry tied to movement initiation, for example, via closed-loop deep-brain stimulation triggered by activity in cortical areas related to motor planning, could be beneficial to patients with Parkinson’s disease.

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