On 2017 Apr 07, Janelia Neural Circuit Computation Journal Club commented:

Highlight/Summary Howe and Dombeck imaged the activity in dopaminergic projection axons from the midbrain to the striatum during self-initiated locomotion and unexpected-reward delivery in mice. They reported a rapid increase in activity, which apparently preceded the locomotion onset. Rapid signalling in these axons was correlated with changes in acceleration during locomotion. Furthermore, axons that carried locomotion signals were found to be distinct from those that responded to unpredicted rewards. The authors concluded that distinct populations of midbrain dopaminergic neurons play a role in locomotion control and processing of unexpected reward.

Strengths This is one of a few studies that uses self-initiated locomotion to contrast dopaminergic signalling during movement-related activity and reward. By imaging separately from axonal projections originating in the substantia nigra (SNc) and ventral tegmental area (VTA), the authors found that the SNc signal was more ‘movement- related’, whereas VTA conveyed both movement and ‘reward-related’ signals. The authors confirmed this observation by describing a hitherto unknown gradient in locomotion associated signal versus reward signal along the dorsal-ventral axis of the striatum, which was consistent with a previously reported pattern of projections from the VTA and SNc to the striatum.

Weaknesses

There are several technical issues that complicates make the interpretation of these results difficult:

Detecting neural activity in individual axons using two-photon calcium imaging could be confounded by brain motion, which is expected to be exacerbated during locomotion. Electrophysiological recordings from the VTA and the SNc during locomotion and reward-delivery could have provided more unambiguous results. In fact, extracellular recordings from the SNc, recorded in a similar task, suggested that movement onset is represented by a pause in firing of SNc neurons (Dodson et al., 2016), rather than by an increase in firing rate.!

The authors reported that the dopaminergic signal preceded locomotion initiation by ~100 msec, as measured indirectly by treadmill acceleration. However, any postural changes or micro-movements, could have started before treadmill movement was detected. Therefore, whether movement initiation precedes or lags behind the dopaminergic signal is unclear based on this data, until more direct measurements of motion initiation are conducted (e.g. EMG, or detailed video analysis of the paws kinematics).

The authors claim that dopaminergic signalling during continuous locomotion were associated with changes in acceleration. However, during locomotion changes in acceleration had a rhythmic pattern at ~3.5 Hz, which complicates the interpretation of whether the dopaminergic signalling reflected past or future changes of the movement pattern. Furthermore, previous studies have reported oscillatory activity in the VTA at 4 Hz (Fujisawa & Buzsaki, 2011), and hence it is unclear whether the rhythmic signalling in the dopaminergic neurons during locomotion reported by Howe and Dombeck could simply reflect a coupling of the activity of the dopaminergic neurons to LFP.

On 2017 Apr 07, Janelia Neural Circuit Computation Journal Club commented:

Highlight/Summary Howe and Dombeck imaged the activity in dopaminergic projection axons from the midbrain to the striatum during self-initiated locomotion and unexpected-reward delivery in mice. They reported a rapid increase in activity, which apparently preceded the locomotion onset. Rapid signalling in these axons was correlated with changes in acceleration during locomotion. Furthermore, axons that carried locomotion signals were found to be distinct from those that responded to unpredicted rewards. The authors concluded that distinct populations of midbrain dopaminergic neurons play a role in locomotion control and processing of unexpected reward.

Strengths This is one of a few studies that uses self-initiated locomotion to contrast dopaminergic signalling during movement-related activity and reward. By imaging separately from axonal projections originating in the substantia nigra (SNc) and ventral tegmental area (VTA), the authors found that the SNc signal was more ‘movement- related’, whereas VTA conveyed both movement and ‘reward-related’ signals. The authors confirmed this observation by describing a hitherto unknown gradient in locomotion associated signal versus reward signal along the dorsal-ventral axis of the striatum, which was consistent with a previously reported pattern of projections from the VTA and SNc to the striatum.

Weaknesses

There are several technical issues that complicates make the interpretation of these results difficult:

Detecting neural activity in individual axons using two-photon calcium imaging could be confounded by brain motion, which is expected to be exacerbated during locomotion. Electrophysiological recordings from the VTA and the SNc during locomotion and reward-delivery could have provided more unambiguous results. In fact, extracellular recordings from the SNc, recorded in a similar task, suggested that movement onset is represented by a pause in firing of SNc neurons (Dodson et al., 2016), rather than by an increase in firing rate.!

The authors reported that the dopaminergic signal preceded locomotion initiation by ~100 msec, as measured indirectly by treadmill acceleration. However, any postural changes or micro-movements, could have started before treadmill movement was detected. Therefore, whether movement initiation precedes or lags behind the dopaminergic signal is unclear based on this data, until more direct measurements of motion initiation are conducted (e.g. EMG, or detailed video analysis of the paws kinematics).

The authors claim that dopaminergic signalling during continuous locomotion were associated with changes in acceleration. However, during locomotion changes in acceleration had a rhythmic pattern at ~3.5 Hz, which complicates the interpretation of whether the dopaminergic signalling reflected past or future changes of the movement pattern. Furthermore, previous studies have reported oscillatory activity in the VTA at 4 Hz (Fujisawa & Buzsaki, 2011), and hence it is unclear whether the rhythmic signalling in the dopaminergic neurons during locomotion reported by Howe and Dombeck could simply reflect a coupling of the activity of the dopaminergic neurons to LFP.