Independent neural coding of reward and movement by pedunculopontine tegmental nucleus neurons in freely navigating rats

Abstract

Phasic firing of dopamine (DA) neurons in the ventral tegmental area (VTA) and substantia nigra (SN) is likely to be crucial for reward processing that guides learning. One of the key structures implicated in the regulation of this DA burst firing is the pedunculopontine tegmental nucleus (PPTg), which projects to both the VTA and SN. Different literatures suggest that the PPTg serves as a sensory-gating area for DA cells or it regulates voluntary movement. This study recorded PPTg single-unit activity as rats perform a spatial navigation task to examine the potential for both reward and movement contributions. PPTg cells showed significant changes in firing relative to reward acquisition, the velocity of movement across the maze and turning behaviors of the rats. Reward, but not movement, correlates were impacted by changes in context, and neither correlate type was affected by reward manipulations (e.g. changing the expected location of a reward). This suggests that the PPTg conjunctively codes both reward and behavioral information, and that the reward information is processed in a context-dependent manner. The distinct anatomical distribution of reward and movement cells emphasizes different models of synaptic control by PPTg of DA burst firing in the VTA and SN. Relevant to both VTA and SN learning systems, however, PPTg appears to serve as a sensory gating mechanism to facilitate reinforcement learning, while at the same time provides reinforcement-based guidance of ongoing goal-directed behaviors.

Figure 1

Behavioral performance. A, The average number of errors in the spatial memory task. Significant differences in the number of errors between blocks were found in the darkness and reward reversal sessions. *p < 0.01, **p < 0.001. B, The probability of choosing large-rewarded arms during the first four choices of the test phases. Rats preferentially selected maze arms associated with large rewards, except during darkness testing and when the small and large reward locations were reversed. All graphs show mean ± SEM.

Figure 2

Single-unit recording in PPTg. A, Locations of recording sites (red dots) in PPTg (light blue). Each dot may represent the location of more than one neuron. B, Illustration of the signals from three simultaneously recorded PPTg cells. The distribution of spike heights on channels 3 and 4 of a recording tetrode are shown on a 2D cluster-cutting space. Analog traces show signals from each tetrode wire for three cells. Scale bar: horizontal, 1 ms; vertical, 0.2 mV.

Figure 3

Peri-event histogram examples of reward-responsive PPTg neurons. A, An example of a neuron showing excited firing to large (left) and small (middle) rewards upon their acquisition (T₀, bin width = 50 ms). The same cell exhibited no change in firing during errors (right). The red line in each histogram indicates the change in velocity during outbound movement. B, An example of a neuron showing inhibited responses to rewards. C, Population summary of the proportion of reward-responsive PPTg neurons. D, Population histogram of reward-excited neurons. The shaded regions indicate SEM. The black bars at the bottom indicate a significant difference in responses between large and small rewards at a given time point (Wilcoxon test, p < 0.05). E, Population histogram of reward-inhibited neurons.

Figure 4

Alteration of reward-related activity after the manipulations of context and reward expectancy. A-D, Peri-event time histograms (bin width = 50 ms, T₀ = reward acquisition) of representative neural responses to rewards before (block 1) and after (block 2) various manipulations. The red line in each histogram shows the change in velocity during outbound movement. Scatter plots depict each neuron's normalized reward activity between blocks. In control sessions, the reward activity was consistent across blocks (A). When darkness was imposed, reward responses changed in magnitude and onset time relative to reward acquisition (B). Here, the reward cells began to fire as the rat approached the location of expected rewards. The reward responses of PPTg neurons did not change significantly after reward locations were switched (C), or when rewards were unexpectedly omitted (D). No change in activity was exhibited in response to the absence of the reward in randomly omitted arms. E, Reward activity change index (RACI) for all reward-responsive cells tested in each manipulation. The asterisk shows that the magnitude of reward responses was significantly altered during the darkness session relative to the other sessions (p < 0.05).

Figure 5

Velocity-correlated activity. A-B, Two examples of neurons whose firing correlated with velocity. Peri-event time histograms (bin width = 50 ms) show that the firing rate of a PPTg cell was increased as the recorded rat moved faster during outbound (left, T₀ = reward acquisition) and turn/inbound movement (middle, T₀ = turn onset) (A). The red line in each histogram shows the velocity of movement. The other cell increased its activity as the rat decreased velocity (B). The right column shows the spatial distribution of cell firing. Vectors indicate the direction of travel, and radius size is proportional to the firing rate in that particular area of the maze. For example, the firing-rate circles occurred at all visited locations except for where velocity was decreased at the end of all arms (A). C, Population summary of the proportion of velocity-correlated PPTg neurons. D, r value change index (RVCI) for velocity-correlated cells recorded in each manipulation. No significant result was found among manipulations (p = 0.98).

Figure 6

Turn-related activity. A-B, Two examples of turn-related PPTg neurons. Peri-event time histograms (bin width = 50 ms) show a PPTg neuron responding to turn movement (middle, T₀ = turn onset), but not to rewards (left, T₀ = reward acquisition) (A). The red line in each histogram illustrates movement velocity. The spatial plots in the right column show increased activity during turn behaviors, and this did not discriminate specific arms or rewards. The other PPTg neuron exhibited dual-encoding of reward and turn response (B). When the same cell was tested in the darkness session, the reward-related activity was reduced, However, the turn-related activity was not changed by the contextual manipulation, C, Population summary of the proportion of turn-related PPTg neurons. D, Turn activity change index (TACI) for turn-related cells recorded in each manipulation. No significant result was found (p = 0.57). E, Population histograms of turn-excited (upper) and turn-inhibited cells (lower).

Figure 7

Distributions of reward- and movement-related PPTg cells along the anterior-posterior axis from -7.44 mm to -8.04 mm to bregma. The four types of behaviorally correlated PPTg cells were distributed throughout all PPTg areas recorded in the current study. However, proportionally more reward-excited cells were found in the anterior part of the PPTg than velocity-correlated and reward-inhibited cells (p values < 0.01). More turn-responsive cells were also recorded in the same subregion than reward-inhibited cell (p = 0.001). These indicate that SN may receive proportionately greater reward excitation and turn signals from the PPTg than does the VTA.